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α5-烟碱型乙酰胆碱受体表达下调对肺癌细胞HIF-1α表达的影响 被引量：5

Effects of dow n-regulated α5-nicotinic acetylcholine receptor expression on HIF-1α expression in lung cancer cells
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摘要 目的通过下调α5-烟碱型乙酰胆碱受体(α5-nAChR)的表达,体外研究尼古丁促肺癌细胞增殖过程中α5-nAChR对缺氧诱导因子(HIF-1α)表达的影响。方法以不同浓度尼古丁作用人肺腺癌细胞株A549,分别采用实时荧光定量PCR和Western blotting检测A549细胞中α5-nAChR、HIF-1αmRNA和蛋白的表达。MTT法、实时荧光定量PCR、Western blotting检测CHRNA5-siRNA转染后,尼古丁促A549细胞增殖的作用和HIF-1α表达的变化。结果尼古丁浓度为1μmol/L时,α5-nAChR和HIF-1α表达明显升高(P<0.05),二者表达呈尼古丁浓度依赖性。CHRNA5-siRNA转染显著抑制α5-nAChR、HIF-1α表达(P<0.05),尼古丁促A549细胞增殖的作用明显受到抑制(P<0.05)。结论α5-nAchR通过调节HIF-1α的表达,在尼古丁促肺癌细胞增殖中起作用,提示α5-nAChR/HIF-1α信号轴可能是吸烟相关性肺癌发生的重要分子机制之一。 Objective To explore the influence of small interfering RNA （siRNA） down-regulated ct5-nicotinic acetyl- choline receptor （ct5-nAChR） expression on hypoxia-induced factor-1 ct （ HIF-1 α ） expression during the process of nico- tine-induced lung cancer A549 cell proliferation in vitro. Methods Expressions of ctS-nAChR and HIF-l~ at mRNA and protein levels in A549 cells were detected by FQ-PCR and Western blotting after treatment with various concentra- tions of nicotine. After CHRNAS-siRNA transfection, nicotine-induced A549 cell proliferation and expression of HIF- 1 oL were detected by MTT, FQ-PCR and Western blotting respectively. Results Expressions of ctS-nAChR and HIF- 1 cx were significantly enhanced with 1 txmol/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 a5-nAchR plays an important role in nicotine-induced A549 cell proliferation via regulating HIF-I a expression, which suggests that α5-nAChR/HIF-1 oL axis may be one of the important molecular mechanisms for nicotine-related lung cancer.
作者 祖珊珊 马晓丽 郏雁飞 赵云 贾颖 肖东杰 汪运山
机构地区 山东大学附属山东大学中心医院中心实验室 山东省肿瘤防治靶向分子研究重点实验室 山东省警官总医院血液净化科
出处 《山东大学学报（医学版）》 CAS 北大核心 2013年第9期8-12,共5页 Journal of Shandong University:Health Sciences
基金 国家自然基金面上项目(81272588) 山东省自然科学基金(ZR2012HM061) 山东省高等学校科技计划(J11LC14) 国家重点基础研究发展计划(973计划)(2012CB966503-4)
关键词 CHRNA5基因 α5-烟碱型乙酰胆碱受体 缺氧诱导因子 尼古丁 肺肿瘤 CHRNA5 gene α5-nicotinic acetylcholine receptor Hypoxia-inducible factor-1 o~ Nicotine Lung neoplasms
分类号 R733 [医药卫生—肿瘤]
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参考文献18

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二级参考文献83

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共引文献36

同被引文献36

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  • 7Liang J,Qian Y,Xu D. Serum tumor markers,hypoxia-inducible factor-1α HIF-1α and vascular endothelial growth factor,in patients with non-small cell lung cancer before and after intervention[J].{H}Asian Pacific Journal of Cancer Prev,2013,(6):3851-3854.
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引证文献5

二级引证文献12

山东大学学报（医学版）
2013年 第9期

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