Hsp70 promotes chemoresistance by blocking Bax mitochondrial translocation in ovarian cancer cells

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• 作者：Xiaokui Yang^a ; ¹ ; Jiandong Wang^a ; ¹ ; Ying Zhou^a ; Yamei Wang^b ; Shuyu Wang^a ; ^{yushu572000@yahoo.com.cn} ; Weiyuan Zhang^a ; ^{zhangwy9921@hotmail.com}
• 关键词：Smac/DIABLO ; second mitochondria-derived activator of caspases/direct IAP binding protein with low pI ; HtrA2 ; high temperature requirement A ; AIF ; apoptosis inducing factor ; IAP ; inhibitor of apoptosis protein ; DMSO ; dimethyl sulfoxide ; BIR ; baculovirus I
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：28 August, 2012
• 卷：321
• 期：2
• 页码：137-143
• 文件大小：692 K

摘要

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.