Relationship between HIF-1α and Autophagy in Targeted Therapy for Lung Cancer

Objective To investigate the relationship between the expression of hypoxia-inducible factor-1α(HIF-1α) and autophagy in human lung adenocarcinoma cell line A549 treated by Gefitinib, which is a molecular-targeting antineoplastic agent. Methods Human lung adenocarcinoma cell line A549 were divided into 4 groups, control group (21% O2, C), Gefitinib group(50 μg/ml, G), hypoxia group (1% O2, H), and Gefitinib + hypoxia group(50 μg/ml Gefitinib, and 1%O2, G+H). All groups were cultured for 24 h. The expression of HIF-1α and MAPLC3-Ⅱ were analyzed by Western blot. Autophagy body was observed by transmission electron microscope. Flow cytometry was used to detect the cell cycle and the apoptotic rate of A549 cell. Results The expression of HIF-1α in Group C and G were (0.24±0.05) and (0.11±0.03), respectively, meanwhile it was significantly increased in Group H (1.34±0.08),moreover it was (0.78±0.04) in Group G + H, lower than that in Group H. The expression of MAPLC3-Ⅱin Group C was (0.85±0.06), and it were increased both in Group G and H (1.32±0.03) and (1.62±0.05), respectively, and it was dramatically increased in Group G + H (1.97±0.04). The number of autophagosomes in Group G, H and G + H were all much more than that in Group C.Cell apoptotic rate in Group C was (7.20±1.80) %,and it was significantly increased in Group G + H (34.4±3.95) %, which was higher than those in Group G and H (20.03±1.12) % and (16.77±1.15) %, respectively. There were statistical significances in the comparison of all above indexes (P<0.05). Conclusion Gefitinib could up-regulate autophagy expression and suppress the hypoxia-induced HIF-1α expression in the anoxic A549 cell. There would be some association between the mechanism of Gefitinib in targeted therapy on NSCLC and the expression of HIF-1α and autophagy.