Beijing Obstetrics and Gynecology Hospital, Capital University of Medical Sciences, Beijing 100026, China.
Cancer Lett. 2012 Aug 28;321(2):137-43. doi: 10.1016/j.canlet.2012.01.030. Epub 2012 Jan 25.
Cisplatin can induce apoptosis in ovarian cancer cells through the mitochondrial death pathway, and dysregulation of this pathway contributes to cisplatin resistance in ovarian cancer cells. Here we show that cisplatin induces mitochondrial proteins such as Smac/DIABLO, Cytochrome c, and HrtA2/Omi release to the cytosol and apoptosis in cisplatin-sensitive, but not -resistant ovarian cancer cells. Bax translocation to mitochondria is required for mitochondrial protein release and cisplatin-induced apoptosis in human ovarian cancer cells. Hsp70 is highly expressed in cisplatin-resistant cells. Hsp70 promotes chemoresistance, in part, by blocking Bax translocation to the mitochondria and mitochondrial protein release to cytosol in human ovarian cancer cells.
顺铂可通过线粒体凋亡途径诱导卵巢癌细胞凋亡，而该途径的失调导致卵巢癌细胞对顺铂产生耐药性。在这里，我们发现顺铂诱导线粒体蛋白如 Smac/DIABLO、细胞色素 c 和 HrtA2/Omi 释放到细胞质中，并在顺铂敏感而非耐药的卵巢癌细胞中诱导凋亡。Bax 易位到线粒体是线粒体蛋白释放和顺铂诱导人卵巢癌细胞凋亡所必需的。热休克蛋白 70 在顺铂耐药细胞中高度表达。热休克蛋白 70 通过阻止 Bax 易位到线粒体和线粒体蛋白释放到细胞质中来促进化疗耐药，部分原因是在人卵巢癌细胞中。
