Objective      Investigate the role of autophagy in the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance in non-small cell lung cancer (NSCLC).       Methods      Stepwise erlotinib selection was used to establish the EGFR-TKI-resistant cell line PER from human NSCLC cell line PC9. Autophagy marker LC3B

P62

and Beclin1 were detected by Western blotting. The influence of autophagy inhibitor chloroquine (CQ) on the drug sensitivity of the PER and PC9 cells was tested. Cell viability was measured by MTT assay and the expres

sion of P-ERKl/2 and P-AKT were measured by Western blotting.       Results      The resistant cell line PER had IC

50

value of 9.6±2.1 μmol/L to erlotinib

192 times higher than that of the PC9 cells (0.05±0.02 μmol/L). The expression of LC3B

P62 and Beclin1 in the PER cells was obviously higher than in the PC9 cells. Cytotoxicity induced by erlotinib was greatly enhanced after autophagy inhibition with CQ. The persist activation of P-ERKl/2 and P-AKT in the PER cells could be inhibited by treatment with CQ.       Conclusion      Autophagy may be involved in EGFR-TKI resistance of NSCLC. Autophagy inhibition thus represents a novel strategy to potentiate erlotinib efficacy in NSCLC treatment.