Salvianolic acid A reverses cisplatin resistance in lung cancer A549 cells by targeting c-met and attenuating Akt/mTOR pathway

Drug resistance is one of the leading causes of chemotherapy failure in non-small cell lung cancer (nsclc) treatment. the purpose of this study was to investigate the role of c-met in human lung cancer cisplatin resistance cell line (a549/ddp) and the reversal mechanism of salvianolic acid a (saa),a phenolic active compound extracted from salvia miltiorrhiza. in this study,we found that a549/ddp cells exert up-regulation of c-met by activating the akt/mtor signaling pathway. we also show that saa could increase the chemotherapeutic efficacy of cisplatin,suggesting a synergistic effect of saa and cisplatin. moreover,we revealed that saa enhanced sensitivity to cisplatin in a549/ddp cells mainly through suppression of the c-met/akt/mtor signaling pathway. knockdown of c-met revealed similar effects as that of saa in a549/ddp cells. in addition,saa effectively prevented multidrug resistance associated protein1 (mdr1) up-regulation in a549/ddp cells. taken together,our results indicated that saa suppressed c-met expression and enhanced the sensitivity of lung adenocarcinoma a549 cells to cisplatin through akt/mtor signaling pathway. © 2017 the authors