s3i-201 Search Results


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  • 96
    Millipore s3i 201
    Superoxide levels (A) in aorta treated with vehicle or Ang II in the presence or absence of <t>S3I-201</t> (P
    S3i 201, supplied by Millipore, used in various techniques. Bioz Stars score: 96/100, based on 403 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/s3i 201/product/Millipore
    Average 96 stars, based on 403 article reviews
    Price from $9.99 to $1999.99
    s3i 201 - by Bioz Stars, 2020-08
    96/100 stars
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    97
    Selleck Chemicals s3i 201
    Effects of STAT3 and NF-κB inhibitors on the expression of components in the Notch signaling cascade in vitro . GBM6 cells were treated with STAT3 (50 μ m WP1066 ( WP ) and 300 μ m <t>S3I-201</t> ( S3I )), NF-κB (10 n m Velcade ( Vel )),
    S3i 201, supplied by Selleck Chemicals, used in various techniques. Bioz Stars score: 97/100, based on 151 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/s3i 201/product/Selleck Chemicals
    Average 97 stars, based on 151 article reviews
    Price from $9.99 to $1999.99
    s3i 201 - by Bioz Stars, 2020-08
    97/100 stars
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    94
    Tocris nsc 74859
    Effects of STAT3 and NF-κB inhibitors on the expression of components in the Notch signaling cascade in vitro . GBM6 cells were treated with STAT3 (50 μ m WP1066 ( WP ) and 300 μ m <t>S3I-201</t> ( S3I )), NF-κB (10 n m Velcade ( Vel )),
    Nsc 74859, supplied by Tocris, used in various techniques. Bioz Stars score: 94/100, based on 2 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/nsc 74859/product/Tocris
    Average 94 stars, based on 2 article reviews
    Price from $9.99 to $1999.99
    nsc 74859 - by Bioz Stars, 2020-08
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    93
    Abcam s3i 201
    CAFs-derived HGF induces EMT and promotes proliferation, migration, and invasion of MET -unamplified GC cells via ERK1/2 and STAT3 signaling. a Downstream oncogenic signals triggered by HGF in MGC803 cells. b Expression of EMT markers in MGC803 cells were detected by western blotting. MGC803 cells were lysed after treatment with recombinant human HGF protein for 2 days or co-cultured with CAFs for 2 days. c Twist1 expression in MGC803 and AGS cells were detected by western blotting. GC cells were pretreated with inhibitors for 6 h, and the same concentration of these inhibitors were added into co-culture system. d Schematic charts of cell growth were measured by CCK-8. GC cells were pretreated with inhibitors for 6 h before they were mixed with CAFs. e Cell migration and invasion of MGC803 and AGS cells with different treatments as indicated were determined using transwell assays. Scale bars, 200 μm. HGF (50 ng/ml); HGFab (300 ng/ml); Crizotinib (0.1 Μm); LY294002 (50 μM); U0126 (20 μM); <t>S3I-201</t> (100 μM). (* P
    S3i 201, supplied by Abcam, used in various techniques. Bioz Stars score: 93/100, based on 12 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/s3i 201/product/Abcam
    Average 93 stars, based on 12 article reviews
    Price from $9.99 to $1999.99
    s3i 201 - by Bioz Stars, 2020-08
    93/100 stars
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    Image Search Results


    Superoxide levels (A) in aorta treated with vehicle or Ang II in the presence or absence of S3I-201 (P

    Journal: Hypertension

    Article Title: SMALL MOLECULE INHIBITORS OF STAT3 PROTECT AGAINST ANGIOTENSIN II-INDUCED VASCULAR DYSFUNCTION AND HYPERTENSION

    doi: 10.1161/HYPERTENSIONAHA.111.00299

    Figure Lengend Snippet: Superoxide levels (A) in aorta treated with vehicle or Ang II in the presence or absence of S3I-201 (P

    Article Snippet: In previous studies, this dose of S3I-201 was well tolerated and induced regression of tumor xenografts with constitutively active STAT3.

    Techniques:

    Responses of carotid arteries (n=7) to acetylcholine (A) and nitroprusside (B) following overnight incubation with vehicle or Ang II in the presence or absence of S3I-201. *P

    Journal: Hypertension

    Article Title: SMALL MOLECULE INHIBITORS OF STAT3 PROTECT AGAINST ANGIOTENSIN II-INDUCED VASCULAR DYSFUNCTION AND HYPERTENSION

    doi: 10.1161/HYPERTENSIONAHA.111.00299

    Figure Lengend Snippet: Responses of carotid arteries (n=7) to acetylcholine (A) and nitroprusside (B) following overnight incubation with vehicle or Ang II in the presence or absence of S3I-201. *P

    Article Snippet: In previous studies, this dose of S3I-201 was well tolerated and induced regression of tumor xenografts with constitutively active STAT3.

    Techniques: Incubation

    Effects of Ang II on arterial blood pressure (n=9)(A) and responses of the carotid artery to acetylcholine (B) following chronic infusion of Ang (1.4 mg kg −1 day −1 ) in mice treated with S3I-201 or vehicle. *P

    Journal: Hypertension

    Article Title: SMALL MOLECULE INHIBITORS OF STAT3 PROTECT AGAINST ANGIOTENSIN II-INDUCED VASCULAR DYSFUNCTION AND HYPERTENSION

    doi: 10.1161/HYPERTENSIONAHA.111.00299

    Figure Lengend Snippet: Effects of Ang II on arterial blood pressure (n=9)(A) and responses of the carotid artery to acetylcholine (B) following chronic infusion of Ang (1.4 mg kg −1 day −1 ) in mice treated with S3I-201 or vehicle. *P

    Article Snippet: In previous studies, this dose of S3I-201 was well tolerated and induced regression of tumor xenografts with constitutively active STAT3.

    Techniques: Mouse Assay

    PD98059 and S3I201 reduced H 2 O 2 –induced ERK1/2 and STAT3 activation, respectively

    Journal: International Journal of Ophthalmology

    Article Title: Activation of the ERK 1/2 and STAT3 signaling pathways is required for 661W cell survival following oxidant injury

    doi: 10.3980/j.issn.2222-3959.2012.02.04

    Figure Lengend Snippet: PD98059 and S3I201 reduced H 2 O 2 –induced ERK1/2 and STAT3 activation, respectively

    Article Snippet: S3I201 and PD98095 were obtained from Calbiochem (San Diego, CA).

    Techniques: Activation Assay

    Charts show periablational and distant tumor VEGF vascular endothelial growth factor and HGF hepatocyte growth factor levels with sham procedure, RFA RF ablation without and with adjuvant STAT3 inhibitor (SI) , and STAT3 inhibitor alone. (a, b) Hepatic RFA RF ablation increased HGF hepatocyte growth factor levels in periablational rim ( a ) and distant tumor ( b ). Adjuvant STAT3 inhibition with S3I-201 did not suppress RFA RF ablation-induced changes in local or distant HGF hepatocyte growth factor levels. Concentration is in picograms per milliliter. (c, d) Conversely, hepatic RFA RF ablation increased periablational rim ( c ) and distant tumor ( d ) VEGF vascular endothelial growth factor levels, which were suppressed with adjuvant STAT3 inhibition—suggesting that RFA RF ablation-induced increases in VEGF vascular endothelial growth factor are mediated through STAT3.

    Journal: Radiology

    Article Title: Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation

    doi: 10.1148/radiol.2017162943

    Figure Lengend Snippet: Charts show periablational and distant tumor VEGF vascular endothelial growth factor and HGF hepatocyte growth factor levels with sham procedure, RFA RF ablation without and with adjuvant STAT3 inhibitor (SI) , and STAT3 inhibitor alone. (a, b) Hepatic RFA RF ablation increased HGF hepatocyte growth factor levels in periablational rim ( a ) and distant tumor ( b ). Adjuvant STAT3 inhibition with S3I-201 did not suppress RFA RF ablation-induced changes in local or distant HGF hepatocyte growth factor levels. Concentration is in picograms per milliliter. (c, d) Conversely, hepatic RFA RF ablation increased periablational rim ( c ) and distant tumor ( d ) VEGF vascular endothelial growth factor levels, which were suppressed with adjuvant STAT3 inhibition—suggesting that RFA RF ablation-induced increases in VEGF vascular endothelial growth factor are mediated through STAT3.

    Article Snippet: Powdered S3I-201 (Sigma-Aldrich), a STAT3 inhibitor, was mixed in 1200 μL of dimethyl sulfoxide to achieve a dose of 10 mg/kg, and 100 μL (per 200-gm animal) was administered by means of intraperitoneal injection at specified times.

    Techniques: Inhibition, Concentration Assay

    Charts show periablational and distant tumor VEGF vascular endothelial growth factor and HGF hepatocyte growth factor levels with sham procedure, RFA RF ablation without and with adjuvant STAT3 inhibitor (SI) , and STAT3 inhibitor alone. (a, b) Hepatic RFA RF ablation increased HGF hepatocyte growth factor levels in periablational rim ( a ) and distant tumor ( b ). Adjuvant STAT3 inhibition with S3I-201 did not suppress RFA RF ablation-induced changes in local or distant HGF hepatocyte growth factor levels. Concentration is in picograms per milliliter. (c, d) Conversely, hepatic RFA RF ablation increased periablational rim ( c ) and distant tumor ( d ) VEGF vascular endothelial growth factor levels, which were suppressed with adjuvant STAT3 inhibition—suggesting that RFA RF ablation-induced increases in VEGF vascular endothelial growth factor are mediated through STAT3.

    Journal: Radiology

    Article Title: Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation

    doi: 10.1148/radiol.2017162943

    Figure Lengend Snippet: Charts show periablational and distant tumor VEGF vascular endothelial growth factor and HGF hepatocyte growth factor levels with sham procedure, RFA RF ablation without and with adjuvant STAT3 inhibitor (SI) , and STAT3 inhibitor alone. (a, b) Hepatic RFA RF ablation increased HGF hepatocyte growth factor levels in periablational rim ( a ) and distant tumor ( b ). Adjuvant STAT3 inhibition with S3I-201 did not suppress RFA RF ablation-induced changes in local or distant HGF hepatocyte growth factor levels. Concentration is in picograms per milliliter. (c, d) Conversely, hepatic RFA RF ablation increased periablational rim ( c ) and distant tumor ( d ) VEGF vascular endothelial growth factor levels, which were suppressed with adjuvant STAT3 inhibition—suggesting that RFA RF ablation-induced increases in VEGF vascular endothelial growth factor are mediated through STAT3.

    Article Snippet: Powdered S3I-201 (Sigma-Aldrich), a STAT3 inhibitor, was mixed in 1200 μL of dimethyl sulfoxide to achieve a dose of 10 mg/kg, and 100 μL (per 200-gm animal) was administered by means of intraperitoneal injection at specified times.

    Techniques: Inhibition, Concentration Assay

    Adjuvant S3I-201, a STAT3 inhibitor (SI) , blocks early (0–7 days) hepatic RFA RF ablation-induced distant tumor growth and increases overall animal end point survival. R = RFA alone, S = sham treatment. (a) Graph shows that adjuvant S3I-201 given immediately after hepatic RFA RF ablation reduces distant R3230 tumor growth compared with hepatic RFA RF ablation alone (R) and to levels even lower than that in animals that received sham procedure ( P

    Journal: Radiology

    Article Title: Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation

    doi: 10.1148/radiol.2017162943

    Figure Lengend Snippet: Adjuvant S3I-201, a STAT3 inhibitor (SI) , blocks early (0–7 days) hepatic RFA RF ablation-induced distant tumor growth and increases overall animal end point survival. R = RFA alone, S = sham treatment. (a) Graph shows that adjuvant S3I-201 given immediately after hepatic RFA RF ablation reduces distant R3230 tumor growth compared with hepatic RFA RF ablation alone (R) and to levels even lower than that in animals that received sham procedure ( P

    Article Snippet: Powdered S3I-201 (Sigma-Aldrich), a STAT3 inhibitor, was mixed in 1200 μL of dimethyl sulfoxide to achieve a dose of 10 mg/kg, and 100 μL (per 200-gm animal) was administered by means of intraperitoneal injection at specified times.

    Techniques:

    Charts show periablational and distant tumor VEGF vascular endothelial growth factor and HGF hepatocyte growth factor levels with sham procedure, RFA RF ablation without and with adjuvant STAT3 inhibitor (SI) , and STAT3 inhibitor alone. (a, b) Hepatic RFA RF ablation increased HGF hepatocyte growth factor levels in periablational rim ( a ) and distant tumor ( b ). Adjuvant STAT3 inhibition with S3I-201 did not suppress RFA RF ablation-induced changes in local or distant HGF hepatocyte growth factor levels. Concentration is in picograms per milliliter. (c, d) Conversely, hepatic RFA RF ablation increased periablational rim ( c ) and distant tumor ( d ) VEGF vascular endothelial growth factor levels, which were suppressed with adjuvant STAT3 inhibition—suggesting that RFA RF ablation-induced increases in VEGF vascular endothelial growth factor are mediated through STAT3.

    Journal: Radiology

    Article Title: Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation

    doi: 10.1148/radiol.2017162943

    Figure Lengend Snippet: Charts show periablational and distant tumor VEGF vascular endothelial growth factor and HGF hepatocyte growth factor levels with sham procedure, RFA RF ablation without and with adjuvant STAT3 inhibitor (SI) , and STAT3 inhibitor alone. (a, b) Hepatic RFA RF ablation increased HGF hepatocyte growth factor levels in periablational rim ( a ) and distant tumor ( b ). Adjuvant STAT3 inhibition with S3I-201 did not suppress RFA RF ablation-induced changes in local or distant HGF hepatocyte growth factor levels. Concentration is in picograms per milliliter. (c, d) Conversely, hepatic RFA RF ablation increased periablational rim ( c ) and distant tumor ( d ) VEGF vascular endothelial growth factor levels, which were suppressed with adjuvant STAT3 inhibition—suggesting that RFA RF ablation-induced increases in VEGF vascular endothelial growth factor are mediated through STAT3.

    Article Snippet: Powdered S3I-201 (Sigma-Aldrich), a STAT3 inhibitor, was mixed in 1200 μL of dimethyl sulfoxide to achieve a dose of 10 mg/kg, and 100 μL (per 200-gm animal) was administered by means of intraperitoneal injection at specified times.

    Techniques: Inhibition, Concentration Assay

    Adjuvant S3I-201, a STAT3 inhibitor (SI) , blocks early (0–7 days) hepatic RFA RF ablation-induced distant tumor growth and increases overall animal end point survival. R = RFA alone, S = sham treatment. (a) Graph shows that adjuvant S3I-201 given immediately after hepatic RFA RF ablation reduces distant R3230 tumor growth compared with hepatic RFA RF ablation alone (R) and to levels even lower than that in animals that received sham procedure ( P

    Journal: Radiology

    Article Title: Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation

    doi: 10.1148/radiol.2017162943

    Figure Lengend Snippet: Adjuvant S3I-201, a STAT3 inhibitor (SI) , blocks early (0–7 days) hepatic RFA RF ablation-induced distant tumor growth and increases overall animal end point survival. R = RFA alone, S = sham treatment. (a) Graph shows that adjuvant S3I-201 given immediately after hepatic RFA RF ablation reduces distant R3230 tumor growth compared with hepatic RFA RF ablation alone (R) and to levels even lower than that in animals that received sham procedure ( P

    Article Snippet: Powdered S3I-201 (Sigma-Aldrich), a STAT3 inhibitor, was mixed in 1200 μL of dimethyl sulfoxide to achieve a dose of 10 mg/kg, and 100 μL (per 200-gm animal) was administered by means of intraperitoneal injection at specified times.

    Techniques:

    Effect of STAT3 Inhibitor S3I-201 on Distant Tumor Growth and Animal End Point Survival

    Journal: Radiology

    Article Title: Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation

    doi: 10.1148/radiol.2017162943

    Figure Lengend Snippet: Effect of STAT3 Inhibitor S3I-201 on Distant Tumor Growth and Animal End Point Survival

    Article Snippet: Powdered S3I-201 (Sigma-Aldrich), a STAT3 inhibitor, was mixed in 1200 μL of dimethyl sulfoxide to achieve a dose of 10 mg/kg, and 100 μL (per 200-gm animal) was administered by means of intraperitoneal injection at specified times.

    Techniques:

    Inhibition of IL-10/STAT3 protects splenocytes against apoptosis induced by chronic stress. WT mice ( n = 5 per group) were pre-treated with SB203580, anti-IL-10R Ab or STAT3 inhibitor S3I-201 as in , before the mice were subjected to chronic

    Journal: Brain, behavior, and immunity

    Article Title: Essential role of IL-10/STAT3 in chronic stress-induced immune suppression

    doi: 10.1016/j.bbi.2013.10.016

    Figure Lengend Snippet: Inhibition of IL-10/STAT3 protects splenocytes against apoptosis induced by chronic stress. WT mice ( n = 5 per group) were pre-treated with SB203580, anti-IL-10R Ab or STAT3 inhibitor S3I-201 as in , before the mice were subjected to chronic

    Article Snippet: To determine the role of IL-10/STAT3 signaling cascade in the chronic stress-induced immune suppression, anti-IL-10R antibody (0.2 mg/ kg, 0.8 mg/ kg or 2 mg/ kg body weight, BioLegend, San Diego, CA) or STAT3 inhibitor S3I-201 (10 mg/ kg body weight, Calbiochem) were given i.p. 2 h before the mice were subjected to chronic restraint stress.

    Techniques: Inhibition, Mouse Assay

    Experiment 2. In a rat isolated heart model, effect of superoxide and STAT3 on IL-10 levels. STAT3 activity was determined by Western blot analysis using the phospho-STAT3 antibody. SIN-1 significantly decreased STAT3 activity and IL-10 levels compared with BP/hADSCs alone. Besides, the administration of S3I-201, a STAT3 inhibitor, significantly decreased IL-10 levels compared with BP/hADSCs alone. *P

    Journal: Redox Biology

    Article Title: Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats

    doi: 10.1016/j.redox.2019.101170

    Figure Lengend Snippet: Experiment 2. In a rat isolated heart model, effect of superoxide and STAT3 on IL-10 levels. STAT3 activity was determined by Western blot analysis using the phospho-STAT3 antibody. SIN-1 significantly decreased STAT3 activity and IL-10 levels compared with BP/hADSCs alone. Besides, the administration of S3I-201, a STAT3 inhibitor, significantly decreased IL-10 levels compared with BP/hADSCs alone. *P

    Article Snippet: Three days after naïve or BP-pretreated hADSCs transplantation into right hamstrings, SHR hearts were isolated and subjected to SIN-1 (37 μM), or S3I-201 (25 μM, 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1Hpyrrole-2,5-dione; Calbiochem, La Jolla, CA, USA).

    Techniques: Isolation, Activity Assay, Western Blot

    Paclitaxel disrupts interaction of STAT3 with tubulin and inhibits STAT3 nucleus translocation. Notes: Cultured NRK-49F cells were treated with 4 μM paclitaxel or 50 mM S3I-201 for 6 to 24 hours, followed by immunoblot for STAT3, p-STAT3, and ECM genes, and immunoprecipitation with antibodies to STAT3 or tubulin. ( A ) Immunoblot analysis of STAT3, p-STAT3, fibronectin, α-SMA, collagen I, and GAPDH after 24 hours of treatment with 50 mM S3I-201. ( B ) Expression levels of fibronectin, α-SMA, and collagen I were quantified by densitometry, and normalized with GAPDH. The density of the bands was quantitated, and p-STAT3 was normalized to STAT3 as a loading control. ( C ) Immunoprecipitates with antibodies to STAT3 were then subjected to immunoblot analysis of STAT3 and p-STAT3, with IgG as input control. ( D ) The density of the bands was quantitated, and p-STAT3 was normalized to STAT3 as a loading control. ( E ) Immunoprecipitates with antibodies to tubulin were then subjected to immunoblot analysis of STAT3, with IgG as input control. ( F ) The density of the bands was quantitated, and STAT3 was normalized to tubulin as a loading control. ( G ) Immunoblot analysis of STAT3 in cytoplasm and nucleus at 6 hours of treatment with paclitaxel. ( H ) The density of the bands was quantitated, and STAT3 was normalized to GAPDH or Lamin B as a loading control. Representative immunoblots from each group (n=8). Data are presented as mean ± SEM. Significant P -values reflecting differences are indicated over the bars (* P

    Journal: Drug Design, Development and Therapy

    Article Title: Paclitaxel attenuates renal interstitial fibroblast activation and interstitial fibrosis by inhibiting STAT3 signaling

    doi: 10.2147/DDDT.S81390

    Figure Lengend Snippet: Paclitaxel disrupts interaction of STAT3 with tubulin and inhibits STAT3 nucleus translocation. Notes: Cultured NRK-49F cells were treated with 4 μM paclitaxel or 50 mM S3I-201 for 6 to 24 hours, followed by immunoblot for STAT3, p-STAT3, and ECM genes, and immunoprecipitation with antibodies to STAT3 or tubulin. ( A ) Immunoblot analysis of STAT3, p-STAT3, fibronectin, α-SMA, collagen I, and GAPDH after 24 hours of treatment with 50 mM S3I-201. ( B ) Expression levels of fibronectin, α-SMA, and collagen I were quantified by densitometry, and normalized with GAPDH. The density of the bands was quantitated, and p-STAT3 was normalized to STAT3 as a loading control. ( C ) Immunoprecipitates with antibodies to STAT3 were then subjected to immunoblot analysis of STAT3 and p-STAT3, with IgG as input control. ( D ) The density of the bands was quantitated, and p-STAT3 was normalized to STAT3 as a loading control. ( E ) Immunoprecipitates with antibodies to tubulin were then subjected to immunoblot analysis of STAT3, with IgG as input control. ( F ) The density of the bands was quantitated, and STAT3 was normalized to tubulin as a loading control. ( G ) Immunoblot analysis of STAT3 in cytoplasm and nucleus at 6 hours of treatment with paclitaxel. ( H ) The density of the bands was quantitated, and STAT3 was normalized to GAPDH or Lamin B as a loading control. Representative immunoblots from each group (n=8). Data are presented as mean ± SEM. Significant P -values reflecting differences are indicated over the bars (* P

    Article Snippet: Reagents and antibodies S3I-201 was purchased from Calbiochem (La Jolla, CA, USA).

    Techniques: Translocation Assay, Cell Culture, Immunoprecipitation, Expressing, Western Blot

    STAT3 activation is enhanced in melanoma tissues of mice treated with Bay60-6583 A and B. phospho-STAT3 (pSTAT3) protein expression analysis in melanoma tissues of mice treated with Bay60-6583 or vehicle (ctr), receiving the STAT3 inhibitor S3I-201 5mg/kg i.p. or vehicle. C. VEGF protein expression analysis in melanoma tissues of mice treated with Bay60-6583 or vehicle and receiving the STAT3 inhibitor S3I-201. D. Melanoma volume was monitored during the treatment with S3I-201 in mice receiving Bay60-6583 or vehicle. Data are from three independent experiments and represent mean ± SEM ( n = 6–12) * p

    Journal: Oncotarget

    Article Title: Myeloid-derived suppressor cells contribute to A2B adenosine receptor-induced VEGF production and angiogenesis in a mouse melanoma model

    doi:

    Figure Lengend Snippet: STAT3 activation is enhanced in melanoma tissues of mice treated with Bay60-6583 A and B. phospho-STAT3 (pSTAT3) protein expression analysis in melanoma tissues of mice treated with Bay60-6583 or vehicle (ctr), receiving the STAT3 inhibitor S3I-201 5mg/kg i.p. or vehicle. C. VEGF protein expression analysis in melanoma tissues of mice treated with Bay60-6583 or vehicle and receiving the STAT3 inhibitor S3I-201. D. Melanoma volume was monitored during the treatment with S3I-201 in mice receiving Bay60-6583 or vehicle. Data are from three independent experiments and represent mean ± SEM ( n = 6–12) * p

    Article Snippet: To block STAT3 signalling S3I-201 (5 mg/kg) (Sigma Aldrich) [ – ] was administered i.p. on day 7 and every two days until endpoint; phosphate-buffered saline containing DMSO was used as control.

    Techniques: Activation Assay, Mouse Assay, Expressing

    IL-2 activates STAT3 pathway to induce the in vitro maturation of hIOs. a ELISA quantification of IL-2, IL-8, TNFα, IL-22, IL-6, IL-1β, IL-11, EGF, OSM, and IL-10 concentrations in the culture supernatant of stimulated and unstimulated Jurkat T cells. Expression of IL-2R subunits as analyzed by RT-PCR b and Western blot analyses c in co-cultured or IL-2-treated hIOs. d Phosphorylation levels of proteins from multiple signaling pathways in control, co-cultured and IL-2-treated hIOs as reported by a human phospho-kinase array (upper panels). Analysis by functional interaction (FI) network highlighted a significant enrichment of phospho-proteins in the mTOR and STAT3 signaling pathways (lower panels). In the FI network, arrows represent activating/catalyzing connections, solid lines ending in a perpendicular line represent inhibition, solid lines represent complexes or inputs and dashed lines represent predicted FI connections. e Representative images of the morphology of hIOs cultured in the presence of 1 ng/ml IL-2, a key component of the co-culture system, or stimulated Jurkat T conditioned medium (CM) with or without IL-2R-inactivating antibodies (anti-IL-2Rβ, anti-IL-2Rγ c ) for two passages. Quantitative assessment of the size of hIOs (left bottom) and the number of budding structure per hIO (right bottom); n = 12 hIOs per group. f Representative Western blot analysis of p-STAT3, p-AKT and p-P70 S6 Kinase levels in co-cultured and IL-2-treated hIOs. g hIOs cultured in the presence of IL-2 (1 ng/ml) with or without the addition of S3I-201 (5 μM), Stattic (1 μM) or Rapamycin (Rapa; 10 nM). Quantitative assessment of the size of hIOs after one passage (14 days) (left bottom) and the number of budding structure per hIO (right bottom); n = 14 hIOs per group. Data are presented as mean values of replicates ± SEM. *** p

    Journal: Nature Communications

    Article Title: Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids

    doi: 10.1038/s41467-018-05450-8

    Figure Lengend Snippet: IL-2 activates STAT3 pathway to induce the in vitro maturation of hIOs. a ELISA quantification of IL-2, IL-8, TNFα, IL-22, IL-6, IL-1β, IL-11, EGF, OSM, and IL-10 concentrations in the culture supernatant of stimulated and unstimulated Jurkat T cells. Expression of IL-2R subunits as analyzed by RT-PCR b and Western blot analyses c in co-cultured or IL-2-treated hIOs. d Phosphorylation levels of proteins from multiple signaling pathways in control, co-cultured and IL-2-treated hIOs as reported by a human phospho-kinase array (upper panels). Analysis by functional interaction (FI) network highlighted a significant enrichment of phospho-proteins in the mTOR and STAT3 signaling pathways (lower panels). In the FI network, arrows represent activating/catalyzing connections, solid lines ending in a perpendicular line represent inhibition, solid lines represent complexes or inputs and dashed lines represent predicted FI connections. e Representative images of the morphology of hIOs cultured in the presence of 1 ng/ml IL-2, a key component of the co-culture system, or stimulated Jurkat T conditioned medium (CM) with or without IL-2R-inactivating antibodies (anti-IL-2Rβ, anti-IL-2Rγ c ) for two passages. Quantitative assessment of the size of hIOs (left bottom) and the number of budding structure per hIO (right bottom); n = 12 hIOs per group. f Representative Western blot analysis of p-STAT3, p-AKT and p-P70 S6 Kinase levels in co-cultured and IL-2-treated hIOs. g hIOs cultured in the presence of IL-2 (1 ng/ml) with or without the addition of S3I-201 (5 μM), Stattic (1 μM) or Rapamycin (Rapa; 10 nM). Quantitative assessment of the size of hIOs after one passage (14 days) (left bottom) and the number of budding structure per hIO (right bottom); n = 14 hIOs per group. Data are presented as mean values of replicates ± SEM. *** p

    Article Snippet: To block IL-2 downstream signal transduction, either the mTOR inhibitor Rapamycin (10 nM; Sigma-Aldrich) or one of the STAT3 inhibitors S3I-201 (10 μM; Sigma-Aldrich) or Stattic (1 μM; Sigma-Aldrich) were also added.

    Techniques: In Vitro, Enzyme-linked Immunosorbent Assay, Expressing, Reverse Transcription Polymerase Chain Reaction, Western Blot, Cell Culture, Functional Assay, Inhibition, Co-Culture Assay

    Administration of the STAT3 kinase inhibitor, S3I-201, delayed renal functional and structural recovery from I/R injury. After administration with or without 10 mg/kg S3I-201 (ST3I) by gavage starting 1 day before I/R injury in wild-type Balb/c mice,

    Journal: Journal of the American Society of Nephrology : JASN

    Article Title: Survivin Mediates Renal Proximal Tubule Recovery from AKI

    doi: 10.1681/ASN.2013010076

    Figure Lengend Snippet: Administration of the STAT3 kinase inhibitor, S3I-201, delayed renal functional and structural recovery from I/R injury. After administration with or without 10 mg/kg S3I-201 (ST3I) by gavage starting 1 day before I/R injury in wild-type Balb/c mice,

    Article Snippet: STAT3 phosphorylation inhibitor S3I-201 was purchased from EMD Millipore Chemicals (Billerica, MA), and the γ-secretase inhibitor RO4929097 was purchased from Selleck Chemicals (Houston, TX).

    Techniques: Functional Assay, Mouse Assay

    The STAT3 kinase inhibitor, S3I-201, decreased STAT3 phosphorylation and survivin expression induced by I/R injury. At different time points after I/R injury in wild-type Balb/c mice, (A) renal cortical lysates were subjected to immunoblotting analysis,

    Journal: Journal of the American Society of Nephrology : JASN

    Article Title: Survivin Mediates Renal Proximal Tubule Recovery from AKI

    doi: 10.1681/ASN.2013010076

    Figure Lengend Snippet: The STAT3 kinase inhibitor, S3I-201, decreased STAT3 phosphorylation and survivin expression induced by I/R injury. At different time points after I/R injury in wild-type Balb/c mice, (A) renal cortical lysates were subjected to immunoblotting analysis,

    Article Snippet: STAT3 phosphorylation inhibitor S3I-201 was purchased from EMD Millipore Chemicals (Billerica, MA), and the γ-secretase inhibitor RO4929097 was purchased from Selleck Chemicals (Houston, TX).

    Techniques: Expressing, Mouse Assay

    STAT-3 appears to regulate the pro-inflammatory response and promote virus replication in H5N1 virus infected chicken and duck cells. (A) Primary chicken embryo cells over-expressing phospho-STAT-3 showed a high phospho-STAT-3 expression while STAT-3 inhibitor S3I-201 treatment resulted in reduced phospho-STAT-3 protein expression in duck cells at 24 h following H5N1-tyEng91 virus infection (1.0 MOI). (B) phospho-STAT-3 over-expressing chicken cells showed a significant reduction in LITAF , IL6 and IL-8 mRNA expression with no significant change in IFN-α expression. (C) At 24 h following H5N1-tyEng91 virus infection, in STAT-3 inhibited duck primary embryo cells, significant increase of LITAF, IL-8 and IL-6 mRNA expression was detected with no significant change in IFN-α expression. Phospho STAT-3 over-expression in chicken cells increased viral replication at 24 h following H5N1-tyEng91 virus infection as evidenced by increased detection of virus NP (A) , matrix gene mRNA (D) and infectious virus output in culture supernatant (E) . STAT-3 inhibition did not significantly affect virus NP (A) matrix gene expression (D) or infectious virus production (E) at 24 h following H5N1-tyEng91 virus infection in duck cells. Relative mRNA expression was determined by real-time PCR to 18S rRNA. Data points are the mean of three biological replicates with error bars as standard deviation (* p

    Journal: Veterinary Research

    Article Title: Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses

    doi: 10.1186/s13567-014-0118-3

    Figure Lengend Snippet: STAT-3 appears to regulate the pro-inflammatory response and promote virus replication in H5N1 virus infected chicken and duck cells. (A) Primary chicken embryo cells over-expressing phospho-STAT-3 showed a high phospho-STAT-3 expression while STAT-3 inhibitor S3I-201 treatment resulted in reduced phospho-STAT-3 protein expression in duck cells at 24 h following H5N1-tyEng91 virus infection (1.0 MOI). (B) phospho-STAT-3 over-expressing chicken cells showed a significant reduction in LITAF , IL6 and IL-8 mRNA expression with no significant change in IFN-α expression. (C) At 24 h following H5N1-tyEng91 virus infection, in STAT-3 inhibited duck primary embryo cells, significant increase of LITAF, IL-8 and IL-6 mRNA expression was detected with no significant change in IFN-α expression. Phospho STAT-3 over-expression in chicken cells increased viral replication at 24 h following H5N1-tyEng91 virus infection as evidenced by increased detection of virus NP (A) , matrix gene mRNA (D) and infectious virus output in culture supernatant (E) . STAT-3 inhibition did not significantly affect virus NP (A) matrix gene expression (D) or infectious virus production (E) at 24 h following H5N1-tyEng91 virus infection in duck cells. Relative mRNA expression was determined by real-time PCR to 18S rRNA. Data points are the mean of three biological replicates with error bars as standard deviation (* p

    Article Snippet: Primary duck embryo cells were treated with STAT-3 inhibitor S3I-201 (Calbiochem, Merck, Nottingham, UK), a cell-permeable amidosalicylic acid compound that binds STAT3-SH2 domain and prevents STAT3 phosphorylation/activation, dimerization and DNA-binding, at a final concentration of 100 μM [ ] or vehicle (DMSO) control, one day before infection.

    Techniques: Infection, Expressing, Over Expression, Inhibition, Real-time Polymerase Chain Reaction, Standard Deviation

    PI3K and STAT3 are required for cmvIL-10-mediated induction of HO-1 and hIL-10. CD14 + monocytes were pretreated with PI3K inhibitor (LY-294002; 50 μM) and STAT3 inhibitor (S3I-201; 50 μM) or with DMSO (Control) for 4 h prior to incubation for 18 h with cmvIL-10. (A) Histograms showing HO-1 and GAPDH levels by intracellular flow cytometry. Open histograms depict results for samples treated with cmvIL-10, and filled histograms depict results for samples treated with DMSO (Control). Dotted-line histograms depict results for samples treated with an isotype control antibody. (B) Graph depicting the intracellular HO-1 mean fluorescence intensity (MFI) values in monocyte cultures treated with cmvIL-10, with or without inhibitors, relative to those of the control. (C) Graph depicting the levels of secreted hIL-10 in monocyte cultures treated with cmvIL-10, with or without inhibitors, relative to those of the control. The number ( N ) of independent biological replicate experiments is shown. Error bars indicate the standard errors of the means. Significant differences between results for test samples and those with the DMSO control were determined using a two-tailed, paired Student's t test and are denoted by asterisks (*, P

    Journal: Journal of Virology

    Article Title: Human Cytomegalovirus-Encoded Human Interleukin-10 (IL-10) Homolog Amplifies Its Immunomodulatory Potential by Upregulating Human IL-10 in Monocytes

    doi: 10.1128/JVI.03066-15

    Figure Lengend Snippet: PI3K and STAT3 are required for cmvIL-10-mediated induction of HO-1 and hIL-10. CD14 + monocytes were pretreated with PI3K inhibitor (LY-294002; 50 μM) and STAT3 inhibitor (S3I-201; 50 μM) or with DMSO (Control) for 4 h prior to incubation for 18 h with cmvIL-10. (A) Histograms showing HO-1 and GAPDH levels by intracellular flow cytometry. Open histograms depict results for samples treated with cmvIL-10, and filled histograms depict results for samples treated with DMSO (Control). Dotted-line histograms depict results for samples treated with an isotype control antibody. (B) Graph depicting the intracellular HO-1 mean fluorescence intensity (MFI) values in monocyte cultures treated with cmvIL-10, with or without inhibitors, relative to those of the control. (C) Graph depicting the levels of secreted hIL-10 in monocyte cultures treated with cmvIL-10, with or without inhibitors, relative to those of the control. The number ( N ) of independent biological replicate experiments is shown. Error bars indicate the standard errors of the means. Significant differences between results for test samples and those with the DMSO control were determined using a two-tailed, paired Student's t test and are denoted by asterisks (*, P

    Article Snippet: The phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 and STAT3 inhibitor VI (S3I-201) (Sigma-Aldrich) were resuspended in dimethyl sulfoxide (DMSO; Sigma-Aldrich).

    Techniques: Incubation, Flow Cytometry, Cytometry, Fluorescence, Two Tailed Test

    Effects of STAT3 and NF-κB inhibitors on the expression of components in the Notch signaling cascade in vitro . GBM6 cells were treated with STAT3 (50 μ m WP1066 ( WP ) and 300 μ m S3I-201 ( S3I )), NF-κB (10 n m Velcade ( Vel )),

    Journal: The Journal of Biological Chemistry

    Article Title: Constitutive Activation of Signal Transducer and Activator of Transcription 3 (STAT3) and Nuclear Factor κB Signaling in Glioblastoma Cancer Stem Cells Regulates the Notch Pathway *

    doi: 10.1074/jbc.M113.477950

    Figure Lengend Snippet: Effects of STAT3 and NF-κB inhibitors on the expression of components in the Notch signaling cascade in vitro . GBM6 cells were treated with STAT3 (50 μ m WP1066 ( WP ) and 300 μ m S3I-201 ( S3I )), NF-κB (10 n m Velcade ( Vel )),

    Article Snippet: We then examined the effects of WP1066 or S3I-201 on the cell viability/proliferation of glioma monolayers and adherent CSCs.

    Techniques: Expressing, In Vitro

    Effects of selective STAT3 inhibitors on adherent glioma CSCs. A , GBM6 cells were treated with WP1066 and S3I-201 at the indicated concentrations, and the expression of STAT3, pSTAT3, and p65 proteins was determined by immunoblotting. Ad-CSC , adherent

    Journal: The Journal of Biological Chemistry

    Article Title: Constitutive Activation of Signal Transducer and Activator of Transcription 3 (STAT3) and Nuclear Factor κB Signaling in Glioblastoma Cancer Stem Cells Regulates the Notch Pathway *

    doi: 10.1074/jbc.M113.477950

    Figure Lengend Snippet: Effects of selective STAT3 inhibitors on adherent glioma CSCs. A , GBM6 cells were treated with WP1066 and S3I-201 at the indicated concentrations, and the expression of STAT3, pSTAT3, and p65 proteins was determined by immunoblotting. Ad-CSC , adherent

    Article Snippet: We then examined the effects of WP1066 or S3I-201 on the cell viability/proliferation of glioma monolayers and adherent CSCs.

    Techniques: Expressing

    STAT3 is required for NRG-induced upregulation of WASF3 When SKBR3 cells were treated with NRG for 30 minutes, there is a significant increase in STAT3 phosphorylation at Tyrosine 705 (Y705) (a). Only a slight increase in STAT3 phosphorylation was seen in the presence of NRG for 10 minutes (a). When these NRG-treated cells are treated with the AG490 JAK2 inhibitor, Y705 activation is suppressed (b). The same suppression is seen when the cells are treated with the either the S3I-201 STAT3 inhibitor, or the Herceptin recombinant, humanized anti-HER2 antibody (b). In STAT3 knockdown SKBR3 cells, NRG does not affect WASF3 expression levels (c). Similarly, knockdown of JAK2 also suppresses NRG-induced expression of WASF3 (d). In the luciferase reporter assay for WASF3, NRG treatment leads to a significant increase in activity, which is suppressed in STAT3 knockdown cells (e). ChIP-qPCR assays show increased levels of STAT3 at the WASF3 promoter-binding site in the presence of NRG (f). ** p

    Journal: Oncogene

    Article Title: WASF3 provides the conduit to facilitate invasion and metastasis in breast cancer cells through HER2/HER3 signaling

    doi: 10.1038/onc.2015.527

    Figure Lengend Snippet: STAT3 is required for NRG-induced upregulation of WASF3 When SKBR3 cells were treated with NRG for 30 minutes, there is a significant increase in STAT3 phosphorylation at Tyrosine 705 (Y705) (a). Only a slight increase in STAT3 phosphorylation was seen in the presence of NRG for 10 minutes (a). When these NRG-treated cells are treated with the AG490 JAK2 inhibitor, Y705 activation is suppressed (b). The same suppression is seen when the cells are treated with the either the S3I-201 STAT3 inhibitor, or the Herceptin recombinant, humanized anti-HER2 antibody (b). In STAT3 knockdown SKBR3 cells, NRG does not affect WASF3 expression levels (c). Similarly, knockdown of JAK2 also suppresses NRG-induced expression of WASF3 (d). In the luciferase reporter assay for WASF3, NRG treatment leads to a significant increase in activity, which is suppressed in STAT3 knockdown cells (e). ChIP-qPCR assays show increased levels of STAT3 at the WASF3 promoter-binding site in the presence of NRG (f). ** p

    Article Snippet: The JAK inhibitor AG490, STAT3 inhibitor S3I-201 and HSP90 inhibitor 17-AAG were obtained from Selleckchem (Houston, TX).

    Techniques: Activation Assay, Recombinant, Expressing, Luciferase, Reporter Assay, Activity Assay, Chromatin Immunoprecipitation, Real-time Polymerase Chain Reaction, Binding Assay

    Activation of STAT1, STAT3 or NFκB by inflammatory cytokines recapitulates kidney aging-related gene expression patterns in human renal epithelial cells. A. The left column of the heat map shows the log 2 fold-changes of 40 direct targets of STAT1 following IFNγ stimulation of HK-2 cells from microarray expression profiling experiments. The right column of the heat map shows the corresponding log 2 -adjusted beta coefficient (age-slope) for these STAT1 direct targets during kidney aging. B. The left column of heat map shows the log 2 fold-changes of 43 direct targets of STAT3 following IL-6 stimulation of HK-2 cells from microarray expression profiling experiments. The middle column shows changes in expression following treatment with the STAT3 inhibitor S3I-201. The right column shows the corresponding log 2 -adjusted beta coefficient (age-slope) during kidney aging. Aging gene expression data are from [ 1 ]. C. The left column of the heat map shows the log 2 fold-changes of 43 direct targets of NFκB following TNFα stimulation of HK-2 cells from microarray expression profiling experiments. The right column of the heat map shows the corresponding log 2 -adjusted beta coefficient (age-slope) for these NFκB direct targets during kidney aging. Yellow indicates increased gene expression (positive fold-change or age-slope) and blue indicates decreased gene expression (negative-fold change or age-slope).

    Journal: PLoS Genetics

    Article Title: The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney

    doi: 10.1371/journal.pgen.1005734

    Figure Lengend Snippet: Activation of STAT1, STAT3 or NFκB by inflammatory cytokines recapitulates kidney aging-related gene expression patterns in human renal epithelial cells. A. The left column of the heat map shows the log 2 fold-changes of 40 direct targets of STAT1 following IFNγ stimulation of HK-2 cells from microarray expression profiling experiments. The right column of the heat map shows the corresponding log 2 -adjusted beta coefficient (age-slope) for these STAT1 direct targets during kidney aging. B. The left column of heat map shows the log 2 fold-changes of 43 direct targets of STAT3 following IL-6 stimulation of HK-2 cells from microarray expression profiling experiments. The middle column shows changes in expression following treatment with the STAT3 inhibitor S3I-201. The right column shows the corresponding log 2 -adjusted beta coefficient (age-slope) during kidney aging. Aging gene expression data are from [ 1 ]. C. The left column of the heat map shows the log 2 fold-changes of 43 direct targets of NFκB following TNFα stimulation of HK-2 cells from microarray expression profiling experiments. The right column of the heat map shows the corresponding log 2 -adjusted beta coefficient (age-slope) for these NFκB direct targets during kidney aging. Yellow indicates increased gene expression (positive fold-change or age-slope) and blue indicates decreased gene expression (negative-fold change or age-slope).

    Article Snippet: We used the drug S3I-201 (Selleck Chemicals) for STAT3 inhibition.

    Techniques: Activation Assay, Expressing, Microarray

    Combined STAT3 inhibition with TPF chemotherapy enhance anti-tumor effect in vivo A. Tumor growth curve and B. representative photo of DTX, CDDP, 5-FU, S3I-201 or combinational chemotherapy. 10 mg/kg DTX or CDDP were infused at day 14 and 15 mg/kg 5-FU was infused every day from day14 to day 19. The S3I-201 only group receive 5 mg/kg S3I-201 every other day and combined group receive additional 5 mg/kg S3I-201 every other day (as indicated by blue ▲) from day 21. n = 5 mice respectively. C. The xenografts from nude mice receiving DTX, CDDP, 5-FU, S3I-201 or combinational chemotherapy and analyzed by CD44 + flow cytometry. D. Quantification of CD44+ population. Data present as mean ± SEM, *, P

    Journal: Oncotarget

    Article Title: STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

    doi:

    Figure Lengend Snippet: Combined STAT3 inhibition with TPF chemotherapy enhance anti-tumor effect in vivo A. Tumor growth curve and B. representative photo of DTX, CDDP, 5-FU, S3I-201 or combinational chemotherapy. 10 mg/kg DTX or CDDP were infused at day 14 and 15 mg/kg 5-FU was infused every day from day14 to day 19. The S3I-201 only group receive 5 mg/kg S3I-201 every other day and combined group receive additional 5 mg/kg S3I-201 every other day (as indicated by blue ▲) from day 21. n = 5 mice respectively. C. The xenografts from nude mice receiving DTX, CDDP, 5-FU, S3I-201 or combinational chemotherapy and analyzed by CD44 + flow cytometry. D. Quantification of CD44+ population. Data present as mean ± SEM, *, P

    Article Snippet: S3I-201 treatment S3I-201 (NSC74859) was purchased from Selleck Chemicals (Westlake Village, CA) and dissolved in dimethyl sulfoxide for use at indicated concentrations.

    Techniques: Inhibition, In Vivo, Mouse Assay, Flow Cytometry, Cytometry

    STAT3 inhibition by S3I-201 in HNSCC CAL27 cell line A. Western blotting of p-STAT3 Tyr705 of HNSCC cell lines as compared with oral keratinocyte cell line (OKC). B. Cell growth of CAL27 was measured using a CCK8 assay after with S3I-201 for 24 h in different concentrations. C. Immunoflurosece shows S3I-201 reduce nuclear expression of p-STAT3 Tyr705 by confocal microscope. D. Representative flow cytometry shows S3I-201 increase apoptosis cells in CAL27 cell line in a dose dependent manner. E. Sphere formation analysis shows S3I-201 decrease CAL27 tumor-sphere formation. Mean ± SEM *, P

    Journal: Oncotarget

    Article Title: STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

    doi:

    Figure Lengend Snippet: STAT3 inhibition by S3I-201 in HNSCC CAL27 cell line A. Western blotting of p-STAT3 Tyr705 of HNSCC cell lines as compared with oral keratinocyte cell line (OKC). B. Cell growth of CAL27 was measured using a CCK8 assay after with S3I-201 for 24 h in different concentrations. C. Immunoflurosece shows S3I-201 reduce nuclear expression of p-STAT3 Tyr705 by confocal microscope. D. Representative flow cytometry shows S3I-201 increase apoptosis cells in CAL27 cell line in a dose dependent manner. E. Sphere formation analysis shows S3I-201 decrease CAL27 tumor-sphere formation. Mean ± SEM *, P

    Article Snippet: S3I-201 treatment S3I-201 (NSC74859) was purchased from Selleck Chemicals (Westlake Village, CA) and dissolved in dimethyl sulfoxide for use at indicated concentrations.

    Techniques: Inhibition, Western Blot, CCK-8 Assay, Expressing, Microscopy, Flow Cytometry, Cytometry

    STAT3 inhibition reduces tumor growth and CSCs in HNSCC xenograft model A. Schematic diagram for the xenograft implantation and drug delivery. STAT3 signaling inhibitor S3I-201 (5 mg/kg) or equivalent volume PBS (control) was given by intraperitoneal injection (i.p) every other day (q.o.d) in CAL27 cells xenograft nude mice for consecutively 14 days ( n = 6 mice, respectively). B. Representative images showed tumor regression in HNSCC xenograft treated with S3I-201 (upper) as compared with control group. Dahs lines were utilized to depict the outline of tumor lump. C. Total tumor volume was assessed in S3I-201 and control treatment every other day. *, P

    Journal: Oncotarget

    Article Title: STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

    doi:

    Figure Lengend Snippet: STAT3 inhibition reduces tumor growth and CSCs in HNSCC xenograft model A. Schematic diagram for the xenograft implantation and drug delivery. STAT3 signaling inhibitor S3I-201 (5 mg/kg) or equivalent volume PBS (control) was given by intraperitoneal injection (i.p) every other day (q.o.d) in CAL27 cells xenograft nude mice for consecutively 14 days ( n = 6 mice, respectively). B. Representative images showed tumor regression in HNSCC xenograft treated with S3I-201 (upper) as compared with control group. Dahs lines were utilized to depict the outline of tumor lump. C. Total tumor volume was assessed in S3I-201 and control treatment every other day. *, P

    Article Snippet: S3I-201 treatment S3I-201 (NSC74859) was purchased from Selleck Chemicals (Westlake Village, CA) and dissolved in dimethyl sulfoxide for use at indicated concentrations.

    Techniques: Inhibition, Injection, Mouse Assay

    Chemotherapeutic treatment of S3I-201 in Tgfbr1/Pten 2cKO mice HNSCC A. Schematic diagram represent S3I-201 delivery strategy in Tgfbr1/Pten 2cKO mice. Oral application of tamoxifen was conducted consecutively 5 days. Mice receive 5 mg/kg S3I-201 or control PBS 100 μl intraperitoneal injection (i.p) every other day (q.o.d) for consecutively 15 days. Data present as mean ± SEM, n = 6, respectively. B. Representative photos show head and neck tumorigenesis was delayed after S3I-201 treatment 15 days as compared with control group. C. Representative photos show tongue tumorigenesis was delayed after S3I-201 treatment 15 days as compared with control group. D. Tumor volume curve showed S3I-201 treatment delay the growth of head and neck tumor; *, P

    Journal: Oncotarget

    Article Title: STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

    doi:

    Figure Lengend Snippet: Chemotherapeutic treatment of S3I-201 in Tgfbr1/Pten 2cKO mice HNSCC A. Schematic diagram represent S3I-201 delivery strategy in Tgfbr1/Pten 2cKO mice. Oral application of tamoxifen was conducted consecutively 5 days. Mice receive 5 mg/kg S3I-201 or control PBS 100 μl intraperitoneal injection (i.p) every other day (q.o.d) for consecutively 15 days. Data present as mean ± SEM, n = 6, respectively. B. Representative photos show head and neck tumorigenesis was delayed after S3I-201 treatment 15 days as compared with control group. C. Representative photos show tongue tumorigenesis was delayed after S3I-201 treatment 15 days as compared with control group. D. Tumor volume curve showed S3I-201 treatment delay the growth of head and neck tumor; *, P

    Article Snippet: S3I-201 treatment S3I-201 (NSC74859) was purchased from Selleck Chemicals (Westlake Village, CA) and dissolved in dimethyl sulfoxide for use at indicated concentrations.

    Techniques: Mouse Assay, Injection

    STAT3 inhibition attenuates chemo reagents enriched CSCs population in vitro A. Representative images of 10 μM cisplatin (CDDP), 10 μM Docetaxel (DTX) and 15 μM 5-fluoracil (5-FU) enrichment side population, which may attenuate by combined treatment of S3I-201. B. Quantification of side population. C. STAT3 inhibition by S3I-201 effectively reduced DTX, CDDP, 5-FU enriched CD44 + population as compared with single reagent counterpart. D. Quantification of side population. Data shown are representative of three individual experiments.

    Journal: Oncotarget

    Article Title: STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

    doi:

    Figure Lengend Snippet: STAT3 inhibition attenuates chemo reagents enriched CSCs population in vitro A. Representative images of 10 μM cisplatin (CDDP), 10 μM Docetaxel (DTX) and 15 μM 5-fluoracil (5-FU) enrichment side population, which may attenuate by combined treatment of S3I-201. B. Quantification of side population. C. STAT3 inhibition by S3I-201 effectively reduced DTX, CDDP, 5-FU enriched CD44 + population as compared with single reagent counterpart. D. Quantification of side population. Data shown are representative of three individual experiments.

    Article Snippet: S3I-201 treatment S3I-201 (NSC74859) was purchased from Selleck Chemicals (Westlake Village, CA) and dissolved in dimethyl sulfoxide for use at indicated concentrations.

    Techniques: Inhibition, In Vitro

    S3I-201 inhibits high glucose-induced STAT3 activation and pro-fibrotic responses in rat renal tubular epithelial cell line. a Time-course of STAT3 phosphorylation (Tyr-705) in rat renal tubular epithelial cells (NRK-52E) stimulated with high glucose (HG; 33 mM); shown is representative Western blot analysis, Ctrl = no glucose control, GAPDH = loading control, n = 4. b Effects of S3I-201 pretreatment on HG-induced STAT3 phosphorylation in NRK-52E cells. Cells were treated with S3I-201 (2.5, 5, and 10 µM) for 1 h, stimulated with HG 30 min, cells collected for Western blot analysis; shown is representative blot from four determinations. c For nuclear localization of p-STAT3, S3I-201 pretreated NRK-52E cells were stimulated with HG for 30 min, and immunofluorescence detection of p-STAT3 (red) evaluated (Methods), DAPI = nuclear fluorescence stain (blue), MERGE = overlaid images, n = 4. Scale bar = 100 μm; 600 × amplification. d , e Fibrosis-related proteins and signaling molecules were detected. Rat renal tubular epithelial cells (NRK-52E) were pretreated with S3I-201 (10 µM) for 1 h and stimulated with HG for 24 h. Representative western blot analysis of TGF-β1, ACE, AT1, and VEGF with GAPDH as loading control; corresponding densitometric analysis of blots, values normalized to loading control GAPDH and reported relative to Ctrl ( d ). Quantitative RT-PCR determination of Collagen IV, TGF-β1 AT1, and ACE mRNA, values normalized to house-keeping gene β-actin and reported relative to Ctrl ( e ). Data are represented as the mean ± SEM of four independent experiments; # p

    Journal: Cell Death & Disease

    Article Title: Inhibition of STAT3 in tubular epithelial cells prevents kidney fibrosis and nephropathy in STZ-induced diabetic mice

    doi: 10.1038/s41419-019-2085-0

    Figure Lengend Snippet: S3I-201 inhibits high glucose-induced STAT3 activation and pro-fibrotic responses in rat renal tubular epithelial cell line. a Time-course of STAT3 phosphorylation (Tyr-705) in rat renal tubular epithelial cells (NRK-52E) stimulated with high glucose (HG; 33 mM); shown is representative Western blot analysis, Ctrl = no glucose control, GAPDH = loading control, n = 4. b Effects of S3I-201 pretreatment on HG-induced STAT3 phosphorylation in NRK-52E cells. Cells were treated with S3I-201 (2.5, 5, and 10 µM) for 1 h, stimulated with HG 30 min, cells collected for Western blot analysis; shown is representative blot from four determinations. c For nuclear localization of p-STAT3, S3I-201 pretreated NRK-52E cells were stimulated with HG for 30 min, and immunofluorescence detection of p-STAT3 (red) evaluated (Methods), DAPI = nuclear fluorescence stain (blue), MERGE = overlaid images, n = 4. Scale bar = 100 μm; 600 × amplification. d , e Fibrosis-related proteins and signaling molecules were detected. Rat renal tubular epithelial cells (NRK-52E) were pretreated with S3I-201 (10 µM) for 1 h and stimulated with HG for 24 h. Representative western blot analysis of TGF-β1, ACE, AT1, and VEGF with GAPDH as loading control; corresponding densitometric analysis of blots, values normalized to loading control GAPDH and reported relative to Ctrl ( d ). Quantitative RT-PCR determination of Collagen IV, TGF-β1 AT1, and ACE mRNA, values normalized to house-keeping gene β-actin and reported relative to Ctrl ( e ). Data are represented as the mean ± SEM of four independent experiments; # p

    Article Snippet: Reagents, cell culture, and treatment S3I-201 was purchased from Selleck Chemicals (Cat no. S1155; Shanghai, China).

    Techniques: Activation Assay, Western Blot, Immunofluorescence, Fluorescence, Staining, Amplification, Quantitative RT-PCR

    STAT3 inhibitor, S3I-201, reduces tissue injury and restores normal function in kidneys of diabetic mice. Diabetes mellitus was induced with STZ in male C57/BL6 mice, two weeks after which, S3I-201 (2.5 mg/kg) was delivered by IP injection for 16 weeks (Methods), n = 7 in each group, Ctrl = citric buffer vehicle control, T1DM = Type 1 diabetes mellitus (DM). Effects of S3I-201 on ( a ) blood glucose (mmol/L) and ( b ) body weight (g) were determined at the indicated weeks. Effects of S3I-201 on STAT3 activation was evaluated by c Immunohistochemical detection of phosphorylated STAT3 (brown) and total STAT3; representative images were shown from seven mice per group; d Quantification of immunohistochemical images using Image J software; values reported as ratio of the control group, n = 7; e Western blot analysis of kidney tissue for phosphorylated STAT3, total STAT3, and loading control GAPDH. Shown is representative from seven determinations. Effects of S3I-201 on kidney status were evaluated by f ratio of kidney/body weight; g urinary albumin (g/L) as index of renal function; h Histological image stained with hematoxylin and eosin (H E) of kidney tissue (arrows indicate structural derangements of tubular epithelia and interstitium), shown is representative from seven determinations, 400× amplification. For a , b , d , f , g , data are presented as means ± SEM, # p

    Journal: Cell Death & Disease

    Article Title: Inhibition of STAT3 in tubular epithelial cells prevents kidney fibrosis and nephropathy in STZ-induced diabetic mice

    doi: 10.1038/s41419-019-2085-0

    Figure Lengend Snippet: STAT3 inhibitor, S3I-201, reduces tissue injury and restores normal function in kidneys of diabetic mice. Diabetes mellitus was induced with STZ in male C57/BL6 mice, two weeks after which, S3I-201 (2.5 mg/kg) was delivered by IP injection for 16 weeks (Methods), n = 7 in each group, Ctrl = citric buffer vehicle control, T1DM = Type 1 diabetes mellitus (DM). Effects of S3I-201 on ( a ) blood glucose (mmol/L) and ( b ) body weight (g) were determined at the indicated weeks. Effects of S3I-201 on STAT3 activation was evaluated by c Immunohistochemical detection of phosphorylated STAT3 (brown) and total STAT3; representative images were shown from seven mice per group; d Quantification of immunohistochemical images using Image J software; values reported as ratio of the control group, n = 7; e Western blot analysis of kidney tissue for phosphorylated STAT3, total STAT3, and loading control GAPDH. Shown is representative from seven determinations. Effects of S3I-201 on kidney status were evaluated by f ratio of kidney/body weight; g urinary albumin (g/L) as index of renal function; h Histological image stained with hematoxylin and eosin (H E) of kidney tissue (arrows indicate structural derangements of tubular epithelia and interstitium), shown is representative from seven determinations, 400× amplification. For a , b , d , f , g , data are presented as means ± SEM, # p

    Article Snippet: Reagents, cell culture, and treatment S3I-201 was purchased from Selleck Chemicals (Cat no. S1155; Shanghai, China).

    Techniques: Mouse Assay, Injection, Activation Assay, Immunohistochemistry, Software, Western Blot, Staining, Amplification

    S3I-201 reduces accumulation of collagen and expression of pro-fibrotic signaling molecules in kidney tissue of diabetic mice. The animal treatment and groups were described in Fig. 1 and Methods section; n = 7 in each group. a Histological depots of collagen fibers (indicated by arrows) as visualized with sirius red staining; shown are representative images from seven mice per group, 400× amplification; b Quantification of collagen accumulation from the sirius red stained images using Image J software; values reported as normalized to Ctrl; c Kidney tissue collagen IV, TGF-β1, ACE, and AT1 mRNA was determined by quantitative RT-PCR; values normalized to the house-keeping gene, β-actin. d Representative Western blot analysis of TGF-β, ACE, AT1, and VEGF in duplicates, GAPDH as loading control. e Corresponding densitometric analysis of blots in e , calculating from densitometric values of repective bands normalized to loading control GAPDH. For b , c , and e , data are presented as means ± SEM; ( n = 7; # p

    Journal: Cell Death & Disease

    Article Title: Inhibition of STAT3 in tubular epithelial cells prevents kidney fibrosis and nephropathy in STZ-induced diabetic mice

    doi: 10.1038/s41419-019-2085-0

    Figure Lengend Snippet: S3I-201 reduces accumulation of collagen and expression of pro-fibrotic signaling molecules in kidney tissue of diabetic mice. The animal treatment and groups were described in Fig. 1 and Methods section; n = 7 in each group. a Histological depots of collagen fibers (indicated by arrows) as visualized with sirius red staining; shown are representative images from seven mice per group, 400× amplification; b Quantification of collagen accumulation from the sirius red stained images using Image J software; values reported as normalized to Ctrl; c Kidney tissue collagen IV, TGF-β1, ACE, and AT1 mRNA was determined by quantitative RT-PCR; values normalized to the house-keeping gene, β-actin. d Representative Western blot analysis of TGF-β, ACE, AT1, and VEGF in duplicates, GAPDH as loading control. e Corresponding densitometric analysis of blots in e , calculating from densitometric values of repective bands normalized to loading control GAPDH. For b , c , and e , data are presented as means ± SEM; ( n = 7; # p

    Article Snippet: Reagents, cell culture, and treatment S3I-201 was purchased from Selleck Chemicals (Cat no. S1155; Shanghai, China).

    Techniques: Expressing, Mouse Assay, Staining, Amplification, Software, Quantitative RT-PCR, Western Blot

    BRG1 regulation of STAT3/VEGFC signaling mediates lymphangiogenesis A. Representative images and quantifications B. of tube formation of human lymphatic endothelial cells (HLECs) cultured with conditioned medium derived from LoVo cells. DMSO was used as vehiche control. Scale bars: 50μm. C. Immunoprecipitation using anti-BRG1 or anti-STAT3 antibodies was performed in LoVo cells, followed by immunoblotting with the indicated antibodies. D. (Left) Western blot analysis of BRG1, STAT3, p-STAT3 expression after transfection with siNC and siBRG1 in the presence or absence of S3I-201 (STAT3-specific inhibitor) in SW480 cells. (Right) Quantitative expression analysis of VEGFC protein levels by ELISA in the supernatants of SW480 cells after transfection with siNC and siBRG1 in the presence or absence of S3I-201 (STAT3-specific inhibitor) in SW480 cells. * p

    Journal: Oncotarget

    Article Title: BRG1 targeting STAT3/VEGFC signaling regulates lymphangiogenesis in colorectal cancer

    doi: 10.18632/oncotarget.9038

    Figure Lengend Snippet: BRG1 regulation of STAT3/VEGFC signaling mediates lymphangiogenesis A. Representative images and quantifications B. of tube formation of human lymphatic endothelial cells (HLECs) cultured with conditioned medium derived from LoVo cells. DMSO was used as vehiche control. Scale bars: 50μm. C. Immunoprecipitation using anti-BRG1 or anti-STAT3 antibodies was performed in LoVo cells, followed by immunoblotting with the indicated antibodies. D. (Left) Western blot analysis of BRG1, STAT3, p-STAT3 expression after transfection with siNC and siBRG1 in the presence or absence of S3I-201 (STAT3-specific inhibitor) in SW480 cells. (Right) Quantitative expression analysis of VEGFC protein levels by ELISA in the supernatants of SW480 cells after transfection with siNC and siBRG1 in the presence or absence of S3I-201 (STAT3-specific inhibitor) in SW480 cells. * p

    Article Snippet: STAT3 inhibitors S3I-201 came from Selleck (Shanghai, China).

    Techniques: Cell Culture, Derivative Assay, Immunoprecipitation, Western Blot, Expressing, Transfection, Enzyme-linked Immunosorbent Assay

    CAFs-derived HGF induces EMT and promotes proliferation, migration, and invasion of MET -unamplified GC cells via ERK1/2 and STAT3 signaling. a Downstream oncogenic signals triggered by HGF in MGC803 cells. b Expression of EMT markers in MGC803 cells were detected by western blotting. MGC803 cells were lysed after treatment with recombinant human HGF protein for 2 days or co-cultured with CAFs for 2 days. c Twist1 expression in MGC803 and AGS cells were detected by western blotting. GC cells were pretreated with inhibitors for 6 h, and the same concentration of these inhibitors were added into co-culture system. d Schematic charts of cell growth were measured by CCK-8. GC cells were pretreated with inhibitors for 6 h before they were mixed with CAFs. e Cell migration and invasion of MGC803 and AGS cells with different treatments as indicated were determined using transwell assays. Scale bars, 200 μm. HGF (50 ng/ml); HGFab (300 ng/ml); Crizotinib (0.1 Μm); LY294002 (50 μM); U0126 (20 μM); S3I-201 (100 μM). (* P

    Journal: Cell Death & Disease

    Article Title: HGF-mediated crosstalk between cancer-associated fibroblasts and MET-unamplified gastric cancer cells activates coordinated tumorigenesis and metastasis

    doi: 10.1038/s41419-018-0922-1

    Figure Lengend Snippet: CAFs-derived HGF induces EMT and promotes proliferation, migration, and invasion of MET -unamplified GC cells via ERK1/2 and STAT3 signaling. a Downstream oncogenic signals triggered by HGF in MGC803 cells. b Expression of EMT markers in MGC803 cells were detected by western blotting. MGC803 cells were lysed after treatment with recombinant human HGF protein for 2 days or co-cultured with CAFs for 2 days. c Twist1 expression in MGC803 and AGS cells were detected by western blotting. GC cells were pretreated with inhibitors for 6 h, and the same concentration of these inhibitors were added into co-culture system. d Schematic charts of cell growth were measured by CCK-8. GC cells were pretreated with inhibitors for 6 h before they were mixed with CAFs. e Cell migration and invasion of MGC803 and AGS cells with different treatments as indicated were determined using transwell assays. Scale bars, 200 μm. HGF (50 ng/ml); HGFab (300 ng/ml); Crizotinib (0.1 Μm); LY294002 (50 μM); U0126 (20 μM); S3I-201 (100 μM). (* P

    Article Snippet: Crizotinib and U0126 from Cell Signaling Technology and S3I-201 from Abcam were used as inhibitors of HGF/c-Met signaling, ERK1/2 signaling and STAT3 signaling pathways, respectively.

    Techniques: Derivative Assay, Migration, Expressing, Western Blot, Recombinant, Cell Culture, Concentration Assay, Co-Culture Assay, CCK-8 Assay

    ODZ10117 does not affect other STAT family members and upstream regulators of STAT3. Cells were incubated for 16 h with vehicle (0.1% DMSO) alone, ODZ10117 (ODZ, 40 μM) or the known STAT3 inhibitors S3I-201 (100 μM), STA-21 (100 μM), nifuroxazide (NIF, 100 μM), napabucasin (NAPA, 4 μM), or AG-490 (150 μM), and then performed immunoblot analysis.

    Journal: Journal of Clinical Medicine

    Article Title: Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

    doi: 10.3390/jcm8111847

    Figure Lengend Snippet: ODZ10117 does not affect other STAT family members and upstream regulators of STAT3. Cells were incubated for 16 h with vehicle (0.1% DMSO) alone, ODZ10117 (ODZ, 40 μM) or the known STAT3 inhibitors S3I-201 (100 μM), STA-21 (100 μM), nifuroxazide (NIF, 100 μM), napabucasin (NAPA, 4 μM), or AG-490 (150 μM), and then performed immunoblot analysis.

    Article Snippet: Reagents The known STAT3 inhibitors S3I-201 [ ], STA-21 [ ], and nifuroxazide [ ] were purchased from Abcam and Sigma-Aldrich.

    Techniques: Incubation

    Molecular docking of ODZ10117 against the SH2 domain of STAT3. ( A ) Docked model of ODZ10117 is shown in stick and the surrounding residues of the SH2 domain of STAT3 are shown by a line model. Hydrogen bonds are shown for Lys591, Arg609, and Ser611. Halogen bond between Cl and Glu612 is shown by a cyan dash. ( B ) Transparent hydrogen bond acceptor/donor surface is shown for surrounding residues. ( C ) 2D-interaction plot is shown and color-coded by various interaction types. ( D ) Superimposed docked models of ODZ10117 (yellow), Pro-pTyr-Leu (cyan), S3I-201 (green), and STA-21 (magenta) over STAT3. (E-H) Docked models of ODZ10117 ( E ), Pro-pTyr-Leu ( F ), S3I-201 ( G ), and STA-21 ( H ) surrounding 4Å residues of STAT3. Color codes for the different types of interactions are shown at the bottom of D.

    Journal: Journal of Clinical Medicine

    Article Title: Development of Oxadiazole-Based ODZ10117 as a Small-Molecule Inhibitor of STAT3 for Targeted Cancer Therapy

    doi: 10.3390/jcm8111847

    Figure Lengend Snippet: Molecular docking of ODZ10117 against the SH2 domain of STAT3. ( A ) Docked model of ODZ10117 is shown in stick and the surrounding residues of the SH2 domain of STAT3 are shown by a line model. Hydrogen bonds are shown for Lys591, Arg609, and Ser611. Halogen bond between Cl and Glu612 is shown by a cyan dash. ( B ) Transparent hydrogen bond acceptor/donor surface is shown for surrounding residues. ( C ) 2D-interaction plot is shown and color-coded by various interaction types. ( D ) Superimposed docked models of ODZ10117 (yellow), Pro-pTyr-Leu (cyan), S3I-201 (green), and STA-21 (magenta) over STAT3. (E-H) Docked models of ODZ10117 ( E ), Pro-pTyr-Leu ( F ), S3I-201 ( G ), and STA-21 ( H ) surrounding 4Å residues of STAT3. Color codes for the different types of interactions are shown at the bottom of D.

    Article Snippet: Reagents The known STAT3 inhibitors S3I-201 [ ], STA-21 [ ], and nifuroxazide [ ] were purchased from Abcam and Sigma-Aldrich.

    Techniques: