西达本胺诱导胰腺癌细胞凋亡

Chidamide Induces Apoptosis of Human Pancreatic Cancer Cells

目的:观察西达本胺对胰腺癌细胞BxPC-3和PANC-1生长抑制及诱导细胞凋亡作用,探讨西达本胺抗胰腺癌的机制。方法:西达本胺处理BxPC-3和PANC-1细胞后,用流式细胞术检测细胞的凋亡率,用罗丹明123和DCFH-DA染色方法测定细胞线粒体膜跨膜电位变化和活性氧(ROS)的产生,用Western印迹检测Bcl-2家族和γH2AX蛋白表达的变化。结果:西达本胺对胰腺癌细胞BxPC-3和PANC-1具有生长抑制和诱导细胞凋亡的作用,且呈时间和剂量依赖关系;处理72 h后,胰腺癌细胞内ROS产生增强导致DNA损伤发生,且线粒体跨膜电位明显下降;促凋亡蛋白Bax的表达,抑制抑凋亡蛋白Bcl-2和Mcl-1的表达。结论:西达本胺具有抑制胰腺癌细胞增殖,诱导细胞凋亡的作用;西达本胺增强胰腺癌细胞内ROS的产生并导致DNA损伤,最终诱导细胞凋亡的发生。

Objective： To determine whether a novel histone deacetylase inhibitor chidamide inhibits proliferation and induces apoptosis of pancreatic cancer cells. Methods： Apoptosis of pancreatic cancer cells BxPC-3 and PANC-1 induced by chidamide were determined by flow eytometry analysis. Mitochondrial membranere potential and ROS production analysis were detected by Rhodamine 123 and DCFH-DA. The effects of ehidamide on ex- pression levels of Bcl-2 family proteins and γH2AX were determined by Western blotting. Results： Chidamide dis-played inhibition activity of cells growth and induction of apoptosis on pancreatic cancer cells. Chidamide induced ROS production resulting in DNA damage accompanied with the loss of mitochondrial membrane potential by regu-lating the expression levels of Bcl-2 family proteins. Conclusion： The results suggest that chidamide may inhibit proliferation and induce apoptosis of pancreatic cancer cells. Chidamine induces ROS production resulting in DNA damage to act the anticancer effects.