TGF-β1 induces erlotinib resistance in non-small cell lung cancer by down-regulating PTEN.

BACKGROUND TKI-acquired resistance is a tough obstacle for effectively treating NSCLC patients with EGFR mutant characteristics. T790M mutations and MET amplifications account for 70% of the acquired resistance, but the causes for the remaining 30% need elucidation. METHODS We detected TGF-β1and PTEN expression levels in 51 NSCLC patients undergoing EGFR-TKI treatment using Immunohistochemistry (IHC) assay. We examined erlotinib sensitivity, apoptosis rate, and invasion ability in PC-9 cells and PC-9/TGF-β1 cells with CCK-8, flow cytometry, and trans-well assays. We examined and analyzed the AKT and ERK pathways' expression levels using western blot. RESULTS High TGF-β1 and low PTEN expression levels were correlated with poor EGFR-TKI sensitivity and overall survival in 51 NSCLC samples. In vitro analysis revealed that TGF-β1 could reduce erlotinib sensitivity, increase anti-apoptosis ability and invasive characteristic in TKI-sensitive PC-9 cell lines by down-regulating PTEN and activating the Akt and ERK pathways. CONCLUSIONS The results suggest that TGF-β1 demonstrated another acquired erlotinib resistance by down-regulating PTEN expression.