Suppression of TGF-β1 enhances chemosensitivity of cisplatin-resistant lung cancer cells through the inhibition of drug-resistant proteins

AbstractCisplatin-based chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC), but drug resistance occurs in most patients, leading to treatment failure. Recent studies have shown that epithelial–mesenchymal transition (EMT) is associated with drug resistance. However, the underlying mechanism is not entirely clear. In this study, first we showed significant positive correlation between the expression of ERCCl and vimentin, and significant negative correlation between the ERCCl and E-cadherin in the neoadjuvant chemotherapy group and the simple surgery group. Second, we showed that cisplatin-resistant A549 cells (A549/DDP) acquire EMT phenotype with high expression of drug-resistant proteins, P-gp and ERCC1. Knockdown of TGF-β1 may reverse EMT and significantly reduce the expression of P-gp and ERCC1. Moreover, A549/DDP cells become more sensitive to cisplatin. In summary, our results globally confirm a molecular and phenotypic association between chemoresistance and EMT of resis...