Journal: Neoplasia (New York, N.Y.)

Article Title: Overcoming Tyrosine Kinase Inhibitor Resistance in Transformed Cell Harboring SEPT9-ABL1 Chimeric Fusion Protein

doi: 10.1016/j.neo.2019.06.001

Figure Lengend Snippet: The effect of the CRM1 inhibitor KPT-330 on SEPT9-ABL1 in vitro . (A) The IC 50 and the dose-response curve of the CRM1 inhibitor KPT-330 in 32D and BaF3 cells expressing BCR-ABL1 or SEPT9-ABL1. The cells were analyzed at 48 hours after starting culture with various concentrations of KPT-330. These experiments were repeated five times, and the median values of IC 50 are shown. Additionally, the representative dose-response curves are shown. (B). The CRM1 expression in 32D cells expressing BCR-ABL1 and SEPT9-ABL1. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib and KPT-330 for 24 hours, the protein expression was evaluated by a Western blot analysis. These experiments were performed three times. (C) The cellular TRP53 distribution in 32D/BCR-ABL1 and 32D/SEPT9-ABL1 treated with KPT-330. After culturewithout treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or combination of imatinib and KPT-330 for 4 hours, the cells were fractionated and evaluated by a Western blot analysis. These experiments were performed three times, and the representative images are shown. (D) The cellular distribution of NFKB1A in 32D cells expressing BCR-ABL1 and SEPT9-ABL1. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib and KPT-330 for 24 hours, the cells were fractionated and evaluated by a Western blot analysis. These experiments were performed three times. (E) The PP2A phosphorylation and SET expression in 32D/BCR-ABL1 and 32D/SEPT9-ABL1 treated with KPT-330 and/or imatinib. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 10 μM, or combination of imatinib and KPT-330 for 24 hours, the protein expressions were evaluated by a Western blot analysis. These experiments were performed three times, and the representative images are shown. The arrows and asterisks indicate the specific and nonspecific bands, respectively. The bars below the images indicated the ratio of p-PP2A/ACTB, PP2A/ACTB, and SET/ACTB in comparison with those from untreated controls in 32D/BCR-ABL1 and 32D/SEPT9-ABL1, whichwere calculated from all the analyzed data. * indicates a P value <.05. (F) The cellular distribution of PP2A and SET in 32D cells expressing BCR-ABL1 and SEPT9-ABL1. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib and KPT-330 for 24 hours, the cells were fractionated and evaluated by a Western blot analysis. These experiments were performed three times. The arrows and asterisks indicate the specific and nonspecific bands, respectively. (G) The TIAM1 expression in 32D/BCR-ABL1 and 32D/SEPT9-ABL1 treated with KPT-330 and/or imatinib. After culture without treatment for controls or with treatment of imatinib 1 μM, KPT-330 1 μM, or combination of imatinib and KPT-330 for 24 hours, the protein expression was evaluated by a Western blot analysis. (H, I) The frequency of Annexin V and PI double-positive cells in 32D cells (D) and BaF3 cells (E) harboring BCR-ABL1 or SEPT9-ABL1 that were cultured without treatment or with imatinib 1 μM, KPT-330 1 μM, or the combination of imatinib 1 μM and KPT-330 1 μM. The analyses were performed 24 hours after treatment using a flow cytometry. These experiments were performed five times. * indicates a P value <.05.

Article Snippet: The CRM1 antagonist, termed a selective inhibitor of nuclear export (SINE), KPT-330 (Selleck Chemicals, Houston, TX) and imatinib (Santa Cruz Biotechnology, Dallas, TX) were dissolved in DMSO at 50 mM for KPT-330 and 100 mM for imatinib.

Techniques: In Vitro, Expressing, Western Blot, Cell Culture, Flow Cytometry

Journal: Neoplasia (New York, N.Y.)

Article Title: Overcoming Tyrosine Kinase Inhibitor Resistance in Transformed Cell Harboring SEPT9-ABL1 Chimeric Fusion Protein

doi: 10.1016/j.neo.2019.06.001

Figure Lengend Snippet: The effect of the CRM1 inhibitor on SEPT9-ABL1 in vivo . The changes in the tumor volume in the subcutaneous tumor model. BALB/c mice transplanted with 5 × 10 6 BaF3/SEPT9-ABL1 cells subcutaneously were treated with imatinib 20 mg/kg daily ( n = 5), KPT-330 5mg/kg 3 times/week ( n 6), or imatinib 20mg/kg daily and KPT-330 5mg/kg 3 times/week ( n = 5) from 10 days after transplantation. The calculated volume of the subcutaneous tumors is indicated at the vertical axis. * indicates a P value <.05. (B) The pathohistology of the involved organs in leukemic mice with BaF3/SEPT9-ABL1 cells. The histological sections stained with hematoxylin and eosin are shown. BaF3/SEPT9-ABL1 cells infiltrated diffusely throughout the bone marrow, predominantly in the red pulp of spleen, and the lobules as well as around the vessels and Glisson's sheath in the liver. * indicates tumor cells. The magnification ratio was showed at 20× in the upper figures and at 100× in the lower figure. The bars indicate 200 μm in the upper figures and 50 μm in the lower figures. (C) The Kaplan-Meier survival curves of the intraperitoneal tumor model. BALB/c mice transplanted with 2 × 10 6 BaF3/SEPT9-ABL1 cells intraperitoneally were treated with vehicle ( n = 3), imatinib 20 mg/kg daily ( n = 7), KPT-330 50 mg/kg 3 times/week ( n = 8), or imatinib 20 mg/kg daily and KPT-330 50 mg/kg 3 times/week ( n = 12) from the day after transplantation. * indicates a P value <.05 (imatinib and KPT-330 vs. imatinib), and **indicates a P value <.05 (imatinib and KPT-330 vs. KPT-330). (D) The Kaplan-Meier survival curves of the intraperitoneal tumor model. BALB/c mice transplanted with 2 10 6 32D/SEPT9-ABL1 cells intraperitoneally were treated with vehicle ( n = 3), imatinib 20 mg/kg daily ( n = 7), KPT-330 50 mg/kg 3 times/week ( n = 7), or imatinib 20 mg/kg daily and KPT-330 50 mg/kg 3 times/week ( n = 8) from the day after transplantation. * indicates a P value <.05 (imatinib and KPT-330 vs. imatinib), **indicates a P value <.05 (imatinib and KPT-330 vs. KPT-330), and ***indicates a P value <.05 (imatinib vs. KPT-330).

Article Snippet: The CRM1 antagonist, termed a selective inhibitor of nuclear export (SINE), KPT-330 (Selleck Chemicals, Houston, TX) and imatinib (Santa Cruz Biotechnology, Dallas, TX) were dissolved in DMSO at 50 mM for KPT-330 and 100 mM for imatinib.

Techniques: In Vivo, Transplantation Assay, Staining

Journal: Frontiers in Oncology

Article Title: Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway

doi: 10.3389/fonc.2026.1762822

Figure Lengend Snippet: Inhibitory effect of combined selinexor and sorafenib on xenograft tumor growth in nude mice. (A) Photographs of final tumor volumes from different treatment groups. (B) Quantitative bar graph of final tumor volumes from different treatment groups. (C) Photographs of the final tumor weights from different treatment groups. (D) Quantitative bar graph of the final tumor weights from different treatment groups. (mean ± SD, n=5; Sel-10 = selinexor monotherapy (10 mg/kg), Sor-10 = sorafenib monotherapy (10 mg/kg), Sel-10 + Sor-10 = selinexor + sorafenib combination (10 mg/kg + 10 mg/kg); *P < 0.05, **P <0.01, ***P <0.001. Statistical analysis was performed using one-way ANOVA followed by LSD- t test). (Refer to Table 1 for detailed measured tumor volume data at key time points during the entire treatment period).

Article Snippet: Selinexor was purchased from Selleck Chemicals, and sorafenib was obtained from MedChemExpress (MCE).

Techniques:

Journal: Frontiers in Oncology

Article Title: Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway

doi: 10.3389/fonc.2026.1762822

Figure Lengend Snippet: Immunohistochemical detection results of related proteins (BAX, Bcl-2, p27, and XPO1) in xenograft tumor tissues of nude mice from different treatment groups. (A) Representative immunohistochemical images of BAX, Bcl-2, p27, and XPO1 expression (magnification=40×; scale bar=50 μm). (B) Quantitative analysis of BAX expression among treatment groups. (C) Quantitative analysis of Bcl-2 expression among treatment groups. (D) Quantitative analysis of p27 expression among treatment groups. (E) Quantitative analysis of XPO1 expression among treatment groups. (Quantitative analysis of immunohistochemical staining intensity: mean ± SD, n=5 fields per section; Sel-10 = selinexor monotherapy (10 mg/kg), Sor-10 = sorafenib monotherapy (10 mg/kg), Sel-10 + Sor-10 = selinexor + sorafenib combination (10 mg/kg + 10 mg/kg); *P < 0.05, **P <0.01, ***P <0.001. Statistical analysis was performed using one-way ANOVA followed by LSD- t test). Coordinated modulation of BAX and Bcl-2 in tumor tissues is consistent with in vitro PUMA upregulation, supporting the functional activation of the BAX/Bcl-2/PUMA apoptotic pathway in vivo (refer to Section 3.1 and Discussion for details).

Article Snippet: Selinexor was purchased from Selleck Chemicals, and sorafenib was obtained from MedChemExpress (MCE).

Techniques: Immunohistochemical staining, Expressing, Staining, In Vitro, Functional Assay, Activation Assay, In Vivo

Journal: Frontiers in Oncology

Article Title: Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway

doi: 10.3389/fonc.2026.1762822

Figure Lengend Snippet: Inhibitory effects of selinexor and sorafenib monotherapy on HCC cell proliferation (CCK-8 assay) (n=3). (A) Inhibitory effect of selinexor at different concentrations on Huh7 cell proliferation (24h, 48h, 72h). (B) Inhibitory effect of sorafenib at different concentrations on Huh7 cell proliferation (24h, 48h, 72h). (C) Inhibitory effect of selinexor at different concentrations on SK-HEP-1 cell proliferation (24h, 48h, 72h). (D) Inhibitory effect of sorafenib at different concentrations on SK-HEP-1 cell proliferation (24h, 48h, 72h). (E) Inhibitory effect of selinexor at different concentrations on HepG2 cell proliferation (24h, 48h, 72h). (F) Inhibitory effect of sorafenib at different concentrations on HepG2 cell proliferation (24h, 48h, 72h). (mean ± SD, n=3 independent experiments; *P < 0.05, **P < 0.01, ***P < 0.001; statistical significance was determined by two-way ANOVA followed by Bonferroni post-hoc test). (The IC 50 values of selinexor and sorafenib against Huh7, SK-HEP-1, and HepG2 cells at 72 h are provided in the main text (Section 3.2)).

Article Snippet: Selinexor was purchased from Selleck Chemicals, and sorafenib was obtained from MedChemExpress (MCE).

Techniques: CCK-8 Assay

Journal: Frontiers in Oncology

Article Title: Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway

doi: 10.3389/fonc.2026.1762822

Figure Lengend Snippet: Inhibitory effects of combined selinexor and sorafenib on HCC cell proliferation (CCK-8 assay) (n=3). (A) Effect of combined selinexor and sorafenib on Huh7 cell proliferation (48h). (B) Effect of combined selinexor and sorafenib on Huh7 cell proliferation (72h). (C) Effect of combined selinexor and sorafenib on SK-HEP-1 cell proliferation (48h). (D) Effect of combined selinexor and sorafenib on SK-HEP-1 cell proliferation (72h). (E) Effect of combined selinexor and sorafenib on HepG2 cell proliferation (48h). (F) Effect of combined selinexor and sorafenib on HepG2 cell proliferation (72h). (mean ± SD, n=3 independent experiments; *P < 0.05, **P < 0.01, ***P < 0.001. Statistical analysis was performed using one-way ANOVA followed by LSD- t test).

Article Snippet: Selinexor was purchased from Selleck Chemicals, and sorafenib was obtained from MedChemExpress (MCE).

Techniques: CCK-8 Assay

Journal: Frontiers in Oncology

Article Title: Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway

doi: 10.3389/fonc.2026.1762822

Figure Lengend Snippet: Regulatory effects of combined selinexor and sorafenib on cell cycle distribution of HCC cells (n=3). (A) Cell cycle distribution of Huh7 cells in the blank control group. (B) Cell cycle distribution of Huh7 cells in the sorafenib group. (C) Cell cycle distribution of Huh7 cells in the selinexor group. (D) Cell cycle distribution of Huh7 cells in the selinexor + sorafenib group. (E) Quantitative analysis of cell cycle distribution in Huh7 cells. (F) Cell cycle distribution of HepG2 cells in the blank control group. (G) Cell cycle distribution of HepG2 cells in the sorafenib group. (H) Cell cycle distribution of HepG2 cells in the selinexor group. (I) Cell cycle distribution of HepG2 cells in the selinexor + sorafenib group. (J) Quantitative analysis of cell cycle distribution in HepG2 cells. (Quantitative analysis of cell cycle phase proportions: mean ± SD, n=3 independent experiments; *P < 0.05, **P < 0.01, ***P < 0.001. Statistical analysis was performed using one-way ANOVA followed by LSD- t test).

Article Snippet: Selinexor was purchased from Selleck Chemicals, and sorafenib was obtained from MedChemExpress (MCE).

Techniques: Control

Journal: Frontiers in Oncology

Article Title: Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway

doi: 10.3389/fonc.2026.1762822

Figure Lengend Snippet: Apoptosis-inducing effects of combined selinexor and sorafenib on HCC cells (n=3). (A) Apoptotic rate of Huh7 cells in the blank control group. (B) Apoptotic rate of Huh7 cells in the sorafenib group. (C) Apoptotic rate of Huh7 cells in the selinexor group. (D) Apoptotic rate of Huh7 cells in the selinexor + sorafenib group. (E) Quantitative analysis of apoptotic rate in Huh7 cells. (F) Apoptotic rate of HepG2 cells in the blank control group. (G) Apoptotic rate of HepG2 cells in the sorafenib group. (H) Apoptotic rate of HepG2 cells in the selinexor group. (I) Apoptotic rate of HepG2 cells in the selinexor + sorafenib group. (J) Quantitative analysis of apoptotic rate in HepG2 cells. (Quantitative analysis of total apoptotic rates (early + late apoptosis): mean ± SD, n=3 independent experiments; *P < 0.05, **P < 0.01, ***P < 0.001. Statistical analysis was performed using one-way ANOVA followed by LSD- t test).

Article Snippet: Selinexor was purchased from Selleck Chemicals, and sorafenib was obtained from MedChemExpress (MCE).

Techniques: Control

Journal: Frontiers in Oncology

Article Title: Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway

doi: 10.3389/fonc.2026.1762822

Figure Lengend Snippet: Effects of combined selinexor and sorafenib on the expression of apoptosis- and cell cycle-related proteins (BAX, Bcl-2, p27, XPO1, PUMA) in Huh7 cells (n=3). (A) The protein expressions of BAX, Bcl-2, p27, XPO1, PUMA by Western Blot. (B) BAX protein data analysis. (C) Bcl-2 protein data analysis. (D) p27 protein data analysis. (E) XPO1 protein data analysis. (F) PUMA protein data analysis. (Quantitative analysis of protein expression levels (normalized to GAPDH): mean ± SD, n=3 independent experiments; *P < 0.05, **P < 0.01, ***P < 0.001. Statistical analysis was performed using one-way ANOVA followed by LSD- t test).

Article Snippet: Selinexor was purchased from Selleck Chemicals, and sorafenib was obtained from MedChemExpress (MCE).

Techniques: Expressing, Western Blot

Journal: Oncogene

Article Title: Runx1/3-driven adaptive endoplasmic reticulum stress pathways contribute to neurofibromagenesis

doi: 10.1038/s41388-023-02620-x

Figure Lengend Snippet: A Interaction between Exportin-1 and p21 in 7 month-old mouse neurofibroma DRG/tumors. B Representative fluorescence images of p21 (green) and Exportin-1 (XPO-1, red) co-localization in human PNFs. DAPI (blue) was used to label nuclei. C Dose response curve showing decreased mouse neurofibroma-derived sphere numbers by treatment of Exportin-1 inhibitor, KPT-330. Three independent experiments were performed. D Time course showing conversely inhibitory effects of Exportin-1 and p21 in nucleus and cytoplasm by KPT-330 (5 μM).

Article Snippet: Reagents GSK2606414 (EMD Millipore, Billerica, MA) and KPT-330 (AdooQ ® Bioscience, Irvine, CA) were dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich).

Techniques: Fluorescence, Derivative Assay