Research Paper Volume 13, Issue 14 pp 18545—18563

The anti-dysenteric drug fraxetin enhances anti-tumor efficacy of gemcitabine and suppresses pancreatic cancer development by antagonizing STAT3 activation

Fraxetin inhibits cellular proliferation and induces mitochondrial-dependent apoptosis in PCCs. (A) The chemical structure of fraxetin. (B, C) The CCK-8 assay was used to assess the viability of hTERT-HPNE, PANC-1 and Patu8988 cells with or without fraxetin treatment (0~200 μM). (D) Real-time cellular analysis (RTCA) was conducted to evaluate the growth of PANC-1 and Patu8988 cells with and without fraxetin treatment. (E) The colony formation assay was used to analyze the proliferation of PANC-1 and Patu8988 cells with and without fraxetin treatment. (F) Immunocytochemical staining of Ki67 in PANC-1 and Patu8988 cells with or without fraxetin treatment. Bar = 50 μm. (G) Flow cytometry analysis for cell apoptosis in PANC-1 and Patu8988 cells with or without fraxetin treatment. (H) Western blot analysis showing the expression of cleaved caspase-8, cleaved caspase-3, Bcl-2, and Bax in PANC-1 and Patu8988 cells with or without fraxetin treatment. Data were presented as the mean ± standard deviation, and were analyzed by One-way ANOVA with Bonferroni’s post-hoc test. **P ***P

Figure 1. Fraxetin inhibits cellular proliferation and induces mitochondrial-dependent apoptosis in PCCs. (A) The chemical structure of fraxetin. (B, C) The CCK-8 assay was used to assess the viability of hTERT-HPNE, PANC-1 and Patu8988 cells with or without fraxetin treatment (0~200 μM). (D) Real-time cellular analysis (RTCA) was conducted to evaluate the growth of PANC-1 and Patu8988 cells with and without fraxetin treatment. (E) The colony formation assay was used to analyze the proliferation of PANC-1 and Patu8988 cells with and without fraxetin treatment. (F) Immunocytochemical staining of Ki67 in PANC-1 and Patu8988 cells with or without fraxetin treatment. Bar = 50 μm. (G) Flow cytometry analysis for cell apoptosis in PANC-1 and Patu8988 cells with or without fraxetin treatment. (H) Western blot analysis showing the expression of cleaved caspase-8, cleaved caspase-3, Bcl-2, and Bax in PANC-1 and Patu8988 cells with or without fraxetin treatment. Data were presented as the mean ± standard deviation, and were analyzed by One-way ANOVA with Bonferroni’s post-hoc test. **P < 0.01, ***P < 0.001.