目的 研究异乌药内酯对人乳腺癌MCF-7细胞生长的抑制作用及其作用机制。方法 体外培养MCF-7细胞，分为对照组及不同浓度异乌药内酯处理组。采用MTT实验检测异乌药内酯对MCF-7细胞增殖的影响；采用流式细胞术和TUNEL染色法检测异乌药内酯对MCF-7细胞周期、线粒体膜电位及细胞凋亡的影响；采用Western blotting法检测与细胞凋亡密切相关的蛋白表达情况。结果 异乌药内酯以时间和剂量依赖性抑制MCF-7细胞增殖、促进细胞凋亡；能够将MCF-7细胞周期阻滞在G₂/M期，诱导线粒体膜电位去极化；上调cleaved Caspase-3和促凋亡蛋白Bax表达，抑制抗凋亡蛋白Bcl-2表达，诱导MCF-7细胞的凋亡。结论 异乌药内酯对MCF-7细胞的增殖抑制作用呈剂量和时间依赖性，其作用机制可能是通过线粒体途径诱导细胞凋亡。

Objective To study the effects and the mechanism of isolinderalactone on inhibiting the growth of human breast cancer MCF-7 cells. Methods Human breast cancer MCF-7 cells were cultured in vitro and treated respectively with indicated concentrations of isolinderalactone by cell culture technique. The proliferation rate was detected by MTT method; Flow cytometry and TUNEL assay were used to observe the effects of isolinderalactone on cell cycle, mitochondrial membrane potential and apoptosis in MCF-7 cells; The apoptosis related protein expression levels were determined by Western blotting. Results Isolinderalactone significantly inhibited the proliferation of MCF-7 cells by inducing cell apoptosis in a time and concentration dependent manner and induced cell cycle arrest at G₂/M phases. The mitochondrial membrane potential was depolarized; And isolinderalactone up-regulated the expressions of apoptosis related proteins Bax and cleaved Caspase-3 and down-regulated the expressions of apoptosis related proteins Bcl-2. Conclusion Isolinderalactone shows obvious anti-cancer activities by inducing cell apoptosis. The mechanism of inducing apoptosis may be associated with the reduction of mitochondrial membrane potential and activation of caspase pathway.

R285.5

国家自然科学基金项目（81473364）；北京市科委科技新星交叉学科项目（xxhz201210）