西达本胺通过线粒体凋亡途径诱导结肠癌HCT-15细胞凋亡

Chidamide induces apoptosis of colon cancer HCT-15 cells through mitochondrial apoptosis pathway

研究西达本胺(Chidamide)对结肠癌细胞系HCT-15的增殖抑制作用及机制.以不同浓度西达本胺处理HCT-15细胞,CCK-8法检测细胞增殖情况及细胞的药物敏感性;平板克隆形成实验检测细胞体外克隆形成能力;流式细胞术检测细胞凋亡;EdU实验检测细胞增殖周期;Western blot检测乙酰化组蛋白、线粒体凋亡途径相关蛋白、细胞周期相关蛋白表达水平的变化.结果表明:西达本胺抑制HCT-15细胞增殖呈浓度和时间依赖性,细胞体外克隆形成能力减弱,凋亡增多,细胞分裂相明显减少、总周期变慢,乙酰化组蛋白H3和H4、线粒体介导的相关凋亡蛋白表达上调、p21、p27表达上调、CDK2、CyclinA2蛋白表达下调.西达本胺可抑制HCT-15细胞增殖,通过线粒体途径诱导细胞凋亡并阻滞细胞周期.

The inhibitory effect and mechanism of Chidamide on the proliferation of colon cancer cell line HCT-15 were studied.HCT-15 were treated with different concentrations of Chidamide,and cell proliferation and drug sensitivity were detected by CCK-8 method;The ability of cell clone formation in vitro was detected by plate clone formation assay.Apoptosis was detected by flow cytometry.The cell cycle was detected by EdU experiment,the expression level of acetylated histone,mitochondrial apoptosis-related proteins,and cell cycle-related proteins were detected by Western blot.The results show that Chidamide inhibited the proliferation of HCT-15 cells in a concentration and time-dependent manner,weakened the ability of cell cloning in vitro,increased apoptosis,significantly reduced the image of cell division,and slowed down the total cycle.The results of western blot showed that acetylated histones H3,H4,mitochondria-mediated apoptosis-related proteins,p21,and p27 were up-regulated.Meanwhile,CDK2 and cyclin A2 were down-regulated.Chidamide could inhibit proliferation,induce apoptosis and block the cell cycle of HCT-15 cells.