Hypoxia-Induced Overexpression Of Alpha Lpha5 Nicotinic Acetylcholine Receptor Of Human Lung Cancer Cell Lines

Previous studies have indicated that alphaS nicotinic acetylcholine receptor (alpha 5-nAChR) is highly associated with lung cancer risk and nicotine dependence. However, the mechanisms through which alpha 5-nAChRs may influence lung carcinogenesis are far from clear. Studies also showed that the ability of nicotine to drive the acquisition of a malignant phenotype characterized by an increased risk of metastasis is mostly similar to that of hypoxia. However, little is known concerning the effects of hypoxia on the expression of HIF-1 alpha and alpha 5-nAChR in human lung cancer cells. In the present study, RT-PCR and western blotting were conducted to assay the mRNA and protein levels of HIF-1 alpha and alpha 5-nAChR under normoxia and hypoxia induced by exposure to 0.5% O-2 for 24 h and 48 h in lung cancer A549 cells. Results showed that hypoxia induced the up regulation of HIF-1 alpha, in a time-dependent manner, which was also observed at the alpha 5-nAChR mRNA and protein levels (P<0.05). A positive correlation was found between HIF-1 alpha, and alpha 5-nAChR expression in both H1975 and H1299 cells. We suggest that hypoxia induced the overexpression of as-nAChR, the mechanism of which may be related to the upregulation of HIF-1 alpha in lung cancer cells. The relationship between HIF-1 alpha and alpha 5-nAChR expression as a possible treatment for lung cancer cells should be assessed in clinical trials.