Inhibition of ZEB1 reverses EMT and chemoresistance in docetaxel-resistant human lung adenocarcinoma cell line



Docetaxel has been used as one of the first-line chemotherapies in solid tumors including advanced non-small cell lung cancer (NSCLC). However, limited responses to chemotherapy are observed in clinic and the molecular mechanisms have not been fully understood. Emerging evidence suggests that epithelial–mesenchymal transition (EMT) plays an important role in the processes of tumor metastasis as well as resistance towards anticancer agents. In this study, it was observed that docetaxel-resistant human lung adenocarcinoma cell line (SPC-A1/DTX) was typical of mesenchymal phenotype. SPC-A1/DTX cell line has increased migratory and invasive capacity both in vitro and in vivo. Among the master EMT-inducing transcriptional factors, ZEB1 was found to be significantly increased in SPC-A1/DTX cell line. ZEB1 knockdown with RNA interference could reverse the EMT phenotype and inhibit the migratory ability of SPC-A1/DTX cells. Furthermore, inhibition of ZEB1 significantly enhanced the chemosensitivity of SPC-A1/DTX cells to docetaxel in vitro and in vivo and ectopic expression of ZEB1 increased the chemoresistance of SPC-A1 cells to docetaxel. All these results provide experimental evidence that ZEB1 might be an attractive target for the treatment of human NSCLC. J. Cell. Biochem. 114: 1395–1403, 2013. © 2013 Wiley Periodicals, Inc.