Docetaxel is recommended as a second-line chemotherapy agent for the non-small-cell lung cancer (NSCLC); however, drug resistance greatly limits its efficiency. Forkhead box M1 (FoxM1), an oncogenic transcription factor, is believed to be involved in the chemoresistance of various human cancers; whereas the association of FoxM1 with acquired docetaxel-resistance in NSCLC remains unclear. In the present study, we investigated the involvement of FoxM1 in the docetaxel-resistant human lung adenocarcinoma A549 cells (A549/DTX). Our results showed that FoxM1 expression was significantly increased in the A549/DTX cells compared with that in the parental A549 cells. FoxM1 siRNA silencing promoted the cytotoxic and pro-apoptotic effect of docetaxel in A549/DTX cells, which was possibly mediated through inducing the activation of c-Jun N-terminal kinases/mitochondrial signaling pathway. Our results suggest a critical role of FoxM1 in docetaxel-resistance of the A549 cells and form the basis for the development of combined therapy of docetaxel and FoxM1 depletion in treating NSCLC.
Keywords: FoxM1; chemoresistance; docetaxel; non-small-cell lung cancer.
© The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.