Journal
CANCER LETTERS
Volume 321, Issue 2, Pages 137-143Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.01.030
Keywords
Hsp70; Bax; Mitochondria; Cisplatin-resistance; Ovarian cancer
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Funding
- Nature Science Funding of China [30872746]
- Nature Science Funding of Beijing [7082034]
- Beijing Municipal Science and Technology Commission [D09060080404491]
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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. (c) 2012 Published by Elsevier Ireland Ltd.
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