Abstract:

Objective   To explore the influence of small interfering RNA (siRNA) down-regulated α5-nicotinic acetylcholine receptor (α5-nAChR) expression on hypoxia-induced factor-1α(HIF-1α) expression during the process of nicotine-induced lung cancer A549 cell proliferation in vitro. Methods    Expressions of α5-nAChR and HIF-1α at mRNA and protein levels in A549 cells were detected by FQ-PCR and Western blotting after treatment with various concentrations of nicotine. After CHRNA5-siRNA transfection, nicotine-induced A549 cell proliferation and expression of HIF-1α were detected by MTT, FQ-PCR and Western blotting respectively. Results   Expressions of α5-nAChR and HIF-1α were significantly enhanced with 1μmol/L nicotine treatment compared with the other concentrations(P<0.05), which presented a nicotine dose-dependent manner. After CHRNA5-siRNA transfection, the expressions of α5-nAChR mRNA and protein decreased obviously(P<0.05). Nicotine-induced A549 cell proliferation was significantly inhibited (P＜0.05). Conclusion    α5-nAchR plays an important role in nicotine-induced A549 cell proliferation via regulating expression, which suggests that α5-nAChR/HIF-1α axis may be one of the important molecular mechanisms for nicotine-related lung cancer.

Key words: CHRNA5 gene；α5-nicotinic acetylcholine receptor；Hypoxia-inducible factor-1α；Nicotine；Lung neoplasms