2-甲基-3-羟基蒽醌诱导人乳腺癌MCF-7细胞凋亡的机制  

2-Methyl-3-hydroxy-anthraquinone induces Ca^(2+)-mediated apoptosis in human MCF-7 breast cancer cells

作　　者：李娜[1] 崔瑞洁[1] 赵小顺[1] 梁金英[2] 

机构地区：[1]新乡市中心医院药剂科,新乡453000 [2]新乡医学院药学院,新乡453000

出　　处：《中国药科大学学报》2011年第4期365-368,共4页Journal of China Pharmaceutical University

摘　　要：为探讨2-甲基-3-羟基蒽醌抗肿瘤作用及其机制,本研究采用锥虫蓝法检测细胞活力,流式细胞仪检测细胞周期变化、细胞凋亡率、线粒体膜电位及细胞内游离钙的变化,Western blot方法检测凋亡相关蛋白caspase-4、caspase-7、caspase-9、Bcl-2、Bax、JNK、细胞色素C的表达。结果发现:2-甲基-3-羟基蒽醌时间依赖性地抑制乳腺癌细胞的生长,升高细胞内游离钙含量,降低线粒体膜电位并诱导其凋亡;药物上调Bax并下调Bcl-2蛋白的表达;诱导caspase-4、caspase-7、caspase-9、calpain的活化及细胞色素C的释放。结果提示2-甲基-3-羟基蒽醌可能通过Ca2+/calpain/caspase-4途径诱导人乳腺癌MCF-7细胞凋亡。To evaluate the mechanism of 2-methyl-3-hydroxy-anthraquinone（MHA） inducing apoptosis inhuman MCF-7 breast cancer cells.Cell viability was assessed by trypan blue dye exclusion assay,cell cycle distri-bution,apoptosis and mitochondrial membrane potential and [Ca2 ＋]i were measured by FACScan;the proteinexpression of caspase-4,caspase-7,caspase-9,Bcl-2,Bax,calpain and cytochrome C in the MCF-7 cells was eval-uated by Western blots.The results demonstrated that MHA was able to inhibit cell proliferation in a time-dependent manner.It induced [Ca2 ＋]i overload,decreased mitochondrial membrane potential and finally in-duced cancer cell apoptosis.Caspase-4,caspase-7,caspase-9 and calpain protein were activated.Bax expressionwas upregulated and Bcl-2 expression was downregulated.MHA induced MCF-7 cells apoptosis via Ca2 ＋ /cal-pain/caspase-4 pathway.

关 键 词：2-甲基-3-羟基蒽醌 凋亡 CASPASE 钙蛋白酶 细胞内游离钙 

分 类 号：R965[医药卫生—药理学]