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七叶皂苷钠通过抑制AKT,ERK上游信号SRC活性诱导人乳腺癌MCF-7细胞凋亡

Keywords: 七叶皂苷钠,细胞凋亡,SRC,AKT,ERK

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Abstract:

探讨七叶皂苷钠对乳腺癌MCF-7细胞的凋亡诱导作用及其可能的作用机制。运用MTT法检测七叶皂苷钠对MCF-7细胞的增殖抑制作用;倒置显微镜观察细胞形态学变化;DAPI染色后在荧光显微镜下检测细胞核变化;采用AnnexinV-FITC/PI流式细胞术检测细胞凋亡率;采用Westernblotting检测凋亡相关蛋白(PARP,cleavedcaspase-8,pro-caspase-3)和细胞存活相关信号分子(AKT,ERK)及其共同上游激酶SRC的磷酸化变化情况。结果显示,不同浓度七叶皂苷钠作用于乳腺癌MCF-7细胞后,以剂量依赖方式抑制MCF-7细胞增殖;诱导细胞凋亡(典型的凋亡形态学变化、细胞核改变和细胞凋亡率显著增加);细胞凋亡相关蛋白PARP切割增加,cleavedcaspase-8表达增加,pro-caspase-3表达减少进一步验证了七叶皂苷钠的凋亡诱导作用;七叶皂苷钠显著抑制细胞存活相关信号分子(AKT,ERK)的磷酸化,其共同上游激酶SRC的活化亦显著下降。结果表明,七叶皂苷钠通过抑制SRC的活化,阻断信号向下游信号分子AKT,ERK的传递,抑制乳腺癌细胞MCF-7增殖,诱导细胞凋亡。

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