cdk inhibitor dinaciclib  (Topscience Co Ltd)

Journal: Cancer biology & therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer.

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Figure 5. Dinaciclib affects the proliferation and size of 3D biliary tract cancer (BTC) spheroids. Viable (A) KKU-100, (B) OCUG-1 and (C) OZ spheroid cells after 96 h stimulation with the indicated dinaciclib concentrations measured with the Promega CellTiter-Glo® 3D cell viability assay. Exemplary pictures of each treatment condition of the different cells are presented (scale bar 500 µm). Values shown indicate concentrations in nM. Data are presented as mean values ± SEM, n = 4 and significances were tested using a one-way analysis of variance (ANOVA), Dunnett’s compared to the untreated control, ****p<.05, *p <.01, **p <.001, ***p <.0001.

Article Snippet: Cyclindependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques: Viability Assay, Control

Journal: Cancer biology & therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer.

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Figure 7. Dinaciclib affects the expression of proteins involved in cell proliferation and tumor progression. (A) Effect of dinaciclib on EGFR and STAT3 protein expression in KKU-100, OCUG-1 and OZ cells. Biliary tract cancer (BTC) cells were either treated with the corresponding IC50 (KKU-100: 8 nM, OCUG-1: 33 nM, OZ: 7 nM), 50 nM (KKU-100) or 100 nM (OCUG-1 and OZ) dinaciclib for 24, 48 and 72 h, respectively. Protein expression was quantified via normalization to corresponding loading controls (figure S7), which were further referred to untreated control cells [x-fold to untreated control = UTC]. Data are presented as mean values ± SEM, n = at least 3 and significances were tested for each dinaciclib concentration against controls using a one-way analysis of variance (ANOVA), Dunnett ****p < .05, *p < .01, **p < .001 and ***p < .0001. (B) Representative immunohistochemical staining of EGFR and STAT3 in the three naïve (untreated) BTC cell lines KKU-100, OCUG-1 and OZ (magnification 400×) showing heterogeneous but overall medium to high expression levels of EGFR and STAT3 in the three BTC cell lines. Data are presented as mean ± SEM of three different areas of the cell blocks.

Article Snippet: Cyclindependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques: Expressing, Control, Concentration Assay, Immunohistochemical staining, Staining

Journal: Cancer Biology & Therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Dinaciclib decreases cell viability dose-dependent in biliary tract cancer (BTC) and one non-tumorigenic cell line. (a) Cell viability of ten malignant BTC cell lines and one non-tumorigenic (MMNK-1) cell line after treatment with increasing dinaciclib concentrations for 72 h. Lines represent the overall fit of the four-parameter logistic regression. (b) IC 50 values including 95% confidence interval (C.I.) were calculated using four-parameter logistic regression. n. d. = not determined.

Article Snippet: Cyclin-dependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques:

Journal: Cancer Biology & Therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Dinaciclib decreases viability, ATP levels, proliferation and induces caspase activity in biliary tract cancer (BTC). (a) ATP levels of KKU-100, OCUG-1 and OZ cells after treatment with dinaciclib concentrations ranging from 0.1–100 nM for 72 h are shown. ATP levels were normalized to the untreated control [% UTC = untreated control]. (b) Time-resolved analysis of KKU-100, OCUG-1 and OZ cell viability after treatment with dinaciclib. Viability was determined after 0, 6, 24, 48 and 72 h of incubation, respectively and normalized to the respective 0 h fluorescence values [% 0 h]. (c) Proliferation of KKU-100, OCUG-1 and OZ cells after treatment with 3.125 nM, corresponding IC 50 or 100 nM dinaciclib. The cellular impedance signal was recorded continuously for 72 h using the unitless parameter cell index that is proportional to the cell number. Shown are representative curves of one biological replicate. (d) Caspase 3/7 levels were measured to detect apoptosis in KKU-100, OCUG-1 and OZ cells after treatment with 3.125 nM, IC 50 and 50 nM dinaciclib for 24, 48 and 72 h. Luminescence values were normalized to UTC [x-fold]. Data are presented as mean values ± SEM, n = 3 and significances were tested using a one-way analysis of variance (ANOVA), Dunnett **** p < .05, * p < .01, ** p < .001 and *** p < .0001.

Article Snippet: Cyclin-dependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques: Activity Assay, Control, Incubation, Fluorescence

Journal: Cancer Biology & Therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Dinaciclib affects the proliferation and size of 3D biliary tract cancer (BTC) spheroids. Viable (A) KKU-100, (B) OCUG-1 and (C) OZ spheroid cells after 96 h stimulation with the indicated dinaciclib concentrations measured with the Promega CellTiter-Glo® 3D cell viability assay. Exemplary pictures of each treatment condition of the different cells are presented (scale bar 500 µm). Values shown indicate concentrations in nM. Data are presented as mean values ± SEM, n = 4 and significances were tested using a one-way analysis of variance (ANOVA), Dunnett’s compared to the untreated control, **** p <.05, * p <.01, ** p <.001, *** p <.0001.

Article Snippet: Cyclin-dependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques: Viability Assay, Control

Journal: Cancer Biology & Therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Dinaciclib affects the expression of genes involved in cell proliferation and tumor progression. The expression of (a) AKT, (b) PTK2, (c) STAT3, (d) ERK and (e) EGFR from treated biliary tract cancer (BTC) cells KKU-100, OCUG-1 and OZ cells is shown each relative to untreated samples. mRNA levels were analyzed following dinaciclib treatment with the respective ½ IC 50 (KKU-100: 4 nM, OCUG-1: 16.5 nM, OZ: 3.5 nM), IC 50 (KKU-100: 8 nM, OCUG-1: 33 nM, OZ: 7 nM) and 50 nM (KKU-100) or 100 nM (OCUG-1 and OZ) for 24 h. Transcript levels were quantified using the delta delta CT method, whereas mRNA levels were first referred to the housekeeping gene GAPDH and treated samples were further normalized to controls. The fold-regulation is the negative inverse of the fold-change, and the respective thresholds for up- and downregulation are depicted as dotted lines. Data are presented as mean values ± SEM, n = 3 and significances were tested for each dinaciclib concentration against controls using a one-way analysis of variance (ANOVA), Dunnett **** p < .05, * p < .01, ** p < .001 and *** p < .0001.

Article Snippet: Cyclin-dependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques: Expressing, Concentration Assay

Journal: Cancer Biology & Therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Dinaciclib affects the expression of proteins involved in cell proliferation and tumor progression. (A) Effect of dinaciclib on EGFR and STAT3 protein expression in KKU-100, OCUG-1 and OZ cells. Biliary tract cancer (BTC) cells were either treated with the corresponding IC 50 (KKU-100: 8 nM, OCUG-1: 33 nM, OZ: 7 nM), 50 nM (KKU-100) or 100 nM (OCUG-1 and OZ) dinaciclib for 24, 48 and 72 h, respectively. Protein expression was quantified via normalization to corresponding loading controls (figure S7), which were further referred to untreated control cells [x-fold to untreated control = UTC]. Data are presented as mean values ± SEM, n = at least 3 and significances were tested for each dinaciclib concentration against controls using a one-way analysis of variance (ANOVA), Dunnett **** p < .05, * p < .01, ** p < .001 and *** p < .0001. (B) Representative immunohistochemical staining of EGFR and STAT3 in the three naïve (untreated) BTC cell lines KKU-100, OCUG-1 and OZ (magnification 400×) showing heterogeneous but overall medium to high expression levels of EGFR and STAT3 in the three BTC cell lines. Data are presented as mean ± SEM of three different areas of the cell blocks.

Article Snippet: Cyclin-dependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques: Expressing, Control, Concentration Assay, Immunohistochemical staining, Staining

Journal: Cancer Biology & Therapy

Article Title: The Cdk inhibitor dinaciclib as a promising anti-tumorigenic agent in biliary tract cancer

doi: 10.1080/15384047.2024.2439057

Figure Lengend Snippet: Dinaciclib reduces the expression of the anti-apoptotic protein Mcl-1 and the phosphorylation at Ser64. Effect of dinaciclib on (A) Mcl-1 and (B) phospho-Mcl-1 (Ser64) protein expression in KKU-100, OCUG-1 and OZ cells. Biliary tract cancer (BTC) cells were either treated with the corresponding IC 50 (KKU-100: 8 nM, OCUG-1: 33 nM, OZ: 7 nM), 50 nM (KKU-100) or 100 nM (OCUG-1 and OZ) dinaciclib for 24, 48 and 72 h, respectively. Protein expression was quantified via normalization to corresponding loading controls (figure S7), which were further referred to untreated control cells [x-fold to untreated control = UTC]. Data are presented as mean values ± SEM, n = at least 3 and significances were tested for each dinaciclib concentration against controls using a one-way analysis of variance (ANOVA), Dunnett **** p < .05, * p < .01, ** p < .001 and *** p < .0001.

Article Snippet: Cyclin-dependent kinase (Cdk) inhibitor dinaciclib as well as cisplatin were purchased from Selleckchem (Houston, TX, USA).

Techniques: Expressing, Phospho-proteomics, Control, Concentration Assay

Journal: Disease Markers

Article Title: CDK Inhibition Reverses Acquired 5-Fluorouracil Resistance in Hepatocellular Carcinoma Cells

doi: 10.1155/2022/6907057

Figure Lengend Snippet: Western blot of BEL7402/5-FU cells with 5-FU treatment (NC) and 5-FU-Dinaciclib-combined treatment (Dinaciclib). p-RB: phosphorylated RB; RB: total RB. (a) Western blot results of p-RB and RB. (b) Gray values of western blot results.

Article Snippet: Cells treated with or without CDK inhibitor Dinaciclib (Topscience Biotechnology, Shanghai, China) were plated in 96-well plates at 2 × 10 3 cells per well.

Techniques: Western Blot

Journal: Disease Markers

Article Title: CDK Inhibition Reverses Acquired 5-Fluorouracil Resistance in Hepatocellular Carcinoma Cells

doi: 10.1155/2022/6907057

Figure Lengend Snippet: Quantity-effect relationship graph of BEL7402/5-FU cells with 5-FU treatment and 5-FU-Dinaciclib combined treatment. The X axis and Y axis show the log transformation of 5-FU concentration and the cell viability, respectively. Error bars show the SE.

Article Snippet: Cells treated with or without CDK inhibitor Dinaciclib (Topscience Biotechnology, Shanghai, China) were plated in 96-well plates at 2 × 10 3 cells per well.

Techniques: Transformation Assay, Concentration Assay

Journal: ACS Infectious Diseases

Article Title: Screening a Library of FDA-Approved and Bioactive Compounds for Antiviral Activity against SARS-CoV-2

doi: 10.1021/acsinfecdis.1c00017

Figure Lengend Snippet: Cell-type-specificity of compounds antiviral activity. Huh-7, HPMEC/hACE2, and Vero-E6 cells were infected with SARS-CoV-2 at MOI 0.05 and treated with (A) GC376 sodium, (B) apilimod mesylate, (C) budesonide, (D) BFH772, (E) dinaciclib, (F) GKT137831, (G) cyclosporin A, (H) B02, and (I) camostat mesylate at indicated concentrations. At 48 hpi, cells were washed, fixed, and stained for SARS-CoV-2 nucleocapsid protein. Plates were fluorescently imaged and analyzed for nucleocapsid stain per nuclei. Relative infection (solid lines) and relative number of cells (dashed lines) are normalized to DMSO-treated wells. Data represent mean ± SEM for n = 4 technical replicates and are representative of n = 3 independent experiments.

Article Snippet: Intriguingly, we found that the CDK inhibitor dinaciclib (EC50 0.13 μM) was more potent in our assays than remdesivir (EC50 2.45 μM) in limiting viral titers in Calu-3 cells as measured by TCID50 and qRT-PCR ( Table ).

Techniques: Activity Assay, Infection, Staining

Journal: bioRxiv

Article Title: Screening a library of FDA-approved and bioactive compounds for antiviral activity against SARS-CoV-2

doi: 10.1101/2020.12.30.424862

Figure Lengend Snippet: Huh7, HPMEC/hACE2 and Vero-E6 cells were infected with SARS-CoV-2 at MOI 0.05 and treated with (A) Dinaciclib, (B) BFH772, (C) Budesonide, (D) GC376 sodium, (E) Apilimod mesylate, (F) GKT137831, (G) Cyclosporin A, (H) B02, and (I) Camostat mesylate at indicated concentrations. At 48hpi cells were washed, fixed, and stained with DAPI and for SARS-CoV-2 nucleocapsid protein. Plates were fluorescently imaged and analyzed for nucleocapsid stain per nuclei. Relative infection (full lines) and relative number of cells (dashed lines) are normalized to DMSO-treated wells. Data represent mean ± SEM for n = 4 technical replicates and are representative of n = 3 independent experiments.

Article Snippet: Of note, a host-directed compound, the cyclin-dependent kinase (CDK) inhibitor dinaciclib, was determined to be more potent than remdesivir in limiting viral replication in human lung epithelial cells.

Techniques: Infection, Staining