Inhibition of mTOR restores cisplatin sensitivity through down-regulation of growth and anti-apoptotic proteins.
作者： Medhi Wangpaichitr , Chunjing Wu , Min You , M.T. Kuo , Lynn Feun
DOI: 10.1016/J.EJPHAR.2008.06.028
关键词:
摘要: We show that cisplatin resistance in certain lung cancer cell lines can be reversed through inhibition of mTOR (mammalian Target Rapamycin). These appear to possess high levels phospho-mTOR, phospho-AKT and other growth-related proteins, such as hTERT (human telomerase reverse transcriptase), Cyclin D3 which decrease upon mTOR. Interestingly one resistant line expresses BCL2/BCLxL, treatment with inhibitor (CCI-779) results decreased these anti-apoptotic proteins may contribute increasing apoptosis. Moreover, continuous exposure CCI-779 was found increase the expression multi-drug P-gp1(P-gycoprotein1) efflux pump therefore should taken into consideration when designing clinical trials this compound.
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