褐藻素通过内质网途径诱导人乳腺癌MCF-7细胞凋亡的实验研究

Fucoxanthin Induces Human MCF-7 Breast Cancer Cells Apoptosis via Endoplasmic Reticulum Pathway

目的探讨褐藻素诱导人乳腺癌MCF-7细胞凋亡及其分子机制。方法以四甲基偶氮唑蓝法检测细胞活力,流式细胞仪检测细胞凋亡率、细胞周期及细胞内游离钙的变化,蛋白质印迹法检测凋亡相关蛋白caspase-4、caspase-7、caspase-9、Bcl-2、Bax、细胞色素C的表达。结果褐藻素剂量依赖性的抑制乳腺癌MCF-7细胞的增殖、升高细胞内游离钙含量,阻滞细胞周期于G0/G1期并诱导其凋亡;上调Bax并下调Bcl-2;诱导caspase-4、caspase-7、caspase-9、钙蛋白酶的活化及细胞色素C的释放。结论褐藻素通过Ca2+/钙蛋白酶/caspase-4途径诱导人乳腺癌MCF-7细胞凋亡。

OBJECTIVE The antiproliferative effects and molecular mechanism of fucoxanthin were evaluated in human MCF-7 breast cancer cells. METHODS Cell viability was assessed by MTT assay; cell cycle distribution, apoptosis and [ Ca2＋ I i were measured by FACScan; the protein expression of caspase-4, caspase-7, caspase-9, Bcl-2, Bax, calpain and cytochrome C in the MCF- 7 cells was evaluated by Western Blotting. RESULTS Fucoxanthiu exerted potent antiproliferative effects, induced [ Ca2＋ ] ~ overload and apoptosis in MCF-7 ceils. Furthermore, fucoxanthin-mediated apoptosis was related with the activation of caspase-4, caspase-7, caspase-9, cytochrome C release from mitochondrion, up-regulation of Bax and calpain, and also down-regulation Bcl-2 in a dose-de- pendent manner. CONCLUSION Fucoxanthin can induce MCF-7 ceils apoptosis via Ca2＋/calpain/caspase-4 pathway.