Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress.

In this study, we found the sensitivity to erlotinib, a well-used EGFR-TKI, was correlated with basal autophagy level. Erlotinib was able to induce autophagy not only in TKI-sensitive, but also TKI-resistant cancer cells. Inhibition of autophagy significantly enhanced cytotoxicity of erlotinib in TKI-resistant cancer cells via modulation of endoplasmic reticulum (ER) stress induced apoptosis. In this process, CCAAT/enhancer binding protein homologous protein (CHOP) acted as an executioner. Downregulation of CHOP with siRNA blocked the autophagy inhibition and erlotinib co-treatment induced apoptosis and prevented cancer cells from this co-treatment-induced cell death. Our findings suggest that autophagy inhibition overcomes erlotinib resistance through modulation of ER stress mediated apoptosis. PMID: 27035631 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/27035631?dopt=Abstract

Source: International Journal of Oncology - March 31, 2016 Category: Cancer & Oncology Authors: Wang Z, Du T, Dong X, Li Z, Wu G, Zhang R Tags: Int J Oncol Source Type: research