Relationship between epithelial to mesenchymal transition and chemoresistance of lung cancer

Objective:The aim of this study was to explore the correlation between epithelial to mesenchymal transition (EMT) and chemoresistance of non-smal-celllung cancer (NSCLC). Methods:In vitro, the drug resistance index of cisplatin resistant lung adenocarcinoma cellline (A549/DDP) was detected by CCK-8 assay;the morphological change between A549/DDP cells and lung adenocarcinoma cells (A549) was observed by phase contrast microscope;expression of EMT markers (including E-cadherin and vimentin) and resistance protein, excision repair cross-complementing 1 (ERCC1) was detected by immunocytochemistry. The expression of E-cadherin, vimentin and ERCC1 was investigated by immunohistochemistry in 120 cases of NSCLC, half of that were treated with pre-operative neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and the other underwent surgery alone (simple surgery group). Results:There was a significant dif erence between the IC50 (half maximal inhibitory concentration) of A549/DDP cells (5.20) and A549 cells (1.88) (P<0.05), and the drug resis-tance index of A549/DDP cells was 2.77. Compared with A549 cells, A549/DDP cells increased expression of ERCC1 (P<0.05). Moreover, A549/DDP cells showed morphological and phenotypic changes consistent with EMT:with spindle-shaped morphology, and decreased expression of E-cadherin and increased expression of vimentin. Immunohistochemistry showed significant positive correlation between the expression of ERCCl and vimentin (r=0.496, 0.332, P<0.05), and significant neg-ative correlation between the ERCCl and E-cadherin (r=-0.403,-0.295, P<0.05) in neoadjuvant chemotherapy group and simple surgery group. In addition, compared with simple surgery group, the expression of ERCC1 (P=0.003) and vimentin (P=0.004) was significantly increased, and the expression of E-cadherin was decreased in neoadjuvant chemotherapy group (P=0.032). Conclusion:A549/DDP cells acquired cisplatin-resistance and occurred EMT simultaneously;the phenomenon of chemoresistance and EMT was caused more easily in neoadjuvant chemotherapy group. As such, we further confirmed the close correlation between chemoresistance and EMT of NSCLC, and provided theoretical basis for the targeting therapy with EMT regulatory factor for chemoresistant NSCLC patients.