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Multidrug Resistance in Hepatoma Cell Line SK-Hep1/CDDP by Modulation of the Mitochondrial Permeability Transition Pore
Yuan Zhou, Xian-Long Ling *, Shi-Wei Li, Bin Yan, Lei Wen
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
Abstract: SK-Hep1/CDDP cell line was induced by pulse treament with a high concentration of cisplatin (CDDP) in vitro. SK-Hep1 and SK-Hep1/CDDP were treated by mitochondrial permeability transition pore (mPTP) reactivator atractyloside (ATR) and mPTP inhibitor cyclosporin (CsA) respectively. Expressions of Mdr-1 and Bax were detected by Western blotting. Apoptosis of the cells was assessed with FITC-Annexin V. Mitochondrial inner membrane potential (DYm) were monitored with fluorescence dry Jc-1. The results showed that mPTP agonist ATR promoted the opening of the mPTP， accelerated the loss of DYm， enhanced apoptosis induced by CDDP， and also increased Bax activity， Whereas mPTP blocker CsA blocked the mPTP， delayed the loss of DYm， inhibited apoptosis induced by CDDP， and also inhibited Bax activity. Meanwhile there was no influence on mdr-1 expression. The results suggested that activation of mPTP might be efficient in clinic trials for cancer treatment and reversal of multidrug resistance.
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