Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncol- ogy. The hypoxia-inducible factor （HIF）-lα plays a crucial role in radiosensitivity, but the detailed mechanisms remain elusive. A relationship has been suggested to exist between hypoxia and autophagy recently. In the current study, we studied the effect of hypoxia-induced autophagy on radioresistance in lung cancer cell lines. A549 and H1299 cells were cultured under normoxia or hypoxia, followed by ir- radiation at dosage ranging from 0 to 8 Gy. Clonogenic assay was performed to calculate surviving frac- tion. EGFP-LC3 plasmid was stably transfected into cells to monitor autopbagic processes. Western blotting was used to evaluate the protein expression levels of HIF-lα, c-Jun, phosphorylated c-Jun, Be- clin 1, LC3 and p62. The mRNA levels of Beclin 1 were detected by qRT-PCR. We found that under hypoxia, both A549 and H1299 cells were radio-resistant compared with normoxia. Hypoxia-induced elevated HIF-1α protein expression preferentially triggered autophagy, accompanied by LC3 induction, EGFP-LC3 puncta and p62 degradation. In the meantime, HIF-1α increased downstream c-Jun phos- phorylation, which in turn upregulated Beclin 1 mRNA and protein expression. The upregulation of Be- clin 1 expression, instead of HIF-1α, could be blocked by SP600125 （a specific inhibitor of c-Jun NH2- terminal kinase）, followed by suppression of autophagy. Under hypoxia, combined treatment of irradia- tion and chloroquine （a potent autophagy inhibitor） significantly decreased the survival potential of lung cancer cells in vitro and in vivo. In conclusion, hypoxia-induced autophagy through evaluating Beclinl expression may be considered as a target to reverse the radioresistance in cancer cells.
