长春新碱对人胃癌BGC细胞增殖与凋亡的影响及其机制

目的通过体内外水平研究长春新碱对人胃癌BGC细胞增殖与凋亡的影响及其机制。方法采用MTS法检测人胃癌BGC细胞的增殖情况;采用Hoechst荧光染色法、流式细胞技术检测细胞凋亡和细胞周期的情况;通过Western blotting法检测BGC细胞内增殖、周期和凋亡相关蛋白表达情况;荷瘤裸鼠实验检测长春新碱抑制胃癌生长情况。结果长春新碱明显抑制BGC细胞的生长,其抑制率与药物浓度呈剂量和时间相关性,将细胞周期阻滞于G1期,并促进其凋亡,下调了细胞增殖和周期相关蛋白p-FAK、FAK、E2F1、Cylin E2、Cyclin D2、CDK2、CDK6的表达,并激活了凋亡相关蛋白Caspase-3。荷瘤裸鼠实验显示长春新碱能明显抑制胃癌生长。结论长春新碱通过下调细胞增殖与周期相关蛋白的表达,使细胞周期在G1期阻滞,同时激活Caspase-3诱导细胞的凋亡。

Effect of vincristine on proliferation inhibiting and apoptosis inducing on BGC cells and study on their mechanisms

Objective The effect and possible mechanism of vincristine on human gastric cancer cell BGC were investigated in in vitro and in vivo experiments. Methods MTS and Hoechst assay was used to evaluate the effects of vincristine on human gastric cancer cell proliferation and apoptosis, respectively. The proliferation of BGC cells was examined by cell proliferation assay; The apoptosis of BGC cells was assayed by Hoechst and flow cytometry; Cell cycle analysis was performed by flow cytometry. The expression level of cell proliferation, cell cycle, and apoptosis related proteins was determined by Western blotting. The treatment effect of vincristine was analyzed in nude mice. Results MTS and Hoechst assay showed vincristine could inhibit the growth of BGCs and promote the apoptosis of BGCs both in time-dependent and dose-dependent manners. The apoptosis rate of BGCs cells increased gradually and the cell cycle was arrested in G1 phase after treated with vincristine. Vincristine could downregulate the expression of phosphorylated- FAK, FAK, E2F1, CylinE2, CyclinD2, CDK2, CDK6, and activate apoptosis-related protein Caspase-3. Vincristine could suppress the growth of human gastric cancer in nude mice. Conclusion Vincristine could inhibit the proliferation and induce the G₁-arrest of BGC cells through its downregulation of cell proliferation and cell cycle related proteins and it also promotes the apoptosis of BGC cells through the activation of Caspase-3.