The role of Axl in drug resistance and epithelial-to-mesenchymal transition of non-small cell lung carcinoma

International Journal of Clinical and Experimental Pathology

Junhe Li¹  Janfeng Wang¹  Changchen Jang¹  Jianping Xiong¹  Fang Wu¹ 

关键词: Axl;    E-cadherin;    N-cadherin;    vimentin;    EMT;    MDR;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Axl, a member of receptor tyrosine kinases (RTKs), has been established as a strong candidate for targeted therapy of cancer. Some reports showed that Axl is a promising therapeutic target to enhance EGFR TKI response in selected EGFR WT NSCLC patients. The present study was aimed to investigate the role of Axl in non-small cell lung carcinoma (NSCLC) drug resistance and the progress of epithelial-to-mesenchymal transition (EMT). MTT was used to detect the cytotoxicity of chemotherapeutic drugs in NSCLC cells, and Western blot to detect the expression of Axl in EGFR wild type NSCLC cell lines. The EMT markers were also determined by Western blot. We found that when downregulating Axl in EGFR WT NSCLC cells, the cells showed a more sensitive response to erlotinib than those overexpressed Axl. The further study showed that when downregulating Axl, the EMT markers E-cadherin was increased while N-cadherin and vimentin were decreased. Those data showed that the inhibition of Axl could reverse the EMT. Combined therapeutic strategies of the inhibitor of Axl and EGFR TKI could be more effective in the treatment of NSCLC drug resistance patients. The EMT signature and Axl might be predictive biomarkers of drug response and therapeutic targets in patients with NSCLC.

【 授权许可】

Unknown