β-榄香烯通过抑制HIF-1α表达促进人肺癌细胞凋亡  

β-Elemene promoted the apoptosis of human lung cancer cells under hypoxia condition via inhibition of HIF-1α protein expression

作　　者：付有政 温华[1] 

机构地区：[1]中国医科大学附属第一医院呼吸内科,沈阳110001 [2]本溪市中心医院呼吸内科,本溪117000

出　　处：《解剖科学进展》2017年第6期634-638,共5页Progress of Anatomical Sciences

基　　金：国家自然科学基金(81170561)

摘　　要：目的探讨β-榄香烯是否通过抑制肺癌细胞中HIF-1α的高表达促进肺癌细胞的凋亡及相关机制。方法常规培养人肺癌A549细胞,实验分为对照组、乏氧组、β-榄香烯组、不同浓度β-榄香烯/乏氧处理组;通过转染含有HIF-1α基因的质粒过表达HIF-1α基因。应用Annexin V-FITC凋亡检测试剂盒及流式细胞仪、TUNEL检测细胞凋亡。并采用免疫荧光检测HIF-1α蛋白的活化、Westen blot方法检测Bax、caspase-3及Bclx L蛋白表达及转染效率。结果β-榄香烯能够抑制肺癌A549细胞的增殖力,呈时间和浓度依赖性,能够诱导乏氧状态下的肺癌A549细胞凋亡。β-榄香烯可通过上调A549细胞的Bax、caspase-3蛋白表达,降低Bcl-xL表达来诱导乏氧状态下肺癌A549的凋亡。此外,β-榄香烯可有效降低乏氧状态下HIF-1α蛋白的高表达。通过转染过表达HIF-1α基因,大大降低了β-榄香烯的诱导凋亡作用。结论β-榄香烯可以上调乏氧状态下A549细胞凋亡,可能与抑制HIF-1α的高表达相关。Objective To investigate the effects of β -Elemene on apoptosis of human lung cancer A549 cells via inhibition of HIF-10L protein expression. Methods A549 cells were eultured and supplemented with 10% FBS, 1% penieillin/streptomyein in 5% CO2 at 37℃. The cells were classified into four groups： control group, 20 μ g/ml β- Elemene group, hypoxia group, hypoxia/10 μg/m1β-Elemene group and hypoxia/20 μg/m1β-Elemene group. The eell apoptosis was assessed by flow cytometry using the Annexin V-FITC/propidium iodide assay kit or TENEL to differentiate the survival and apoptotic eells. Bax, Bcl-xL, easpase-3 and HIF-1 a proteins expressions were detected by Western blot or immunofluoreseenee staining. Results β-Elemene inhibited the proliferation of A549 eells in a dose-time dependent manner, induced the apoptosis of the eells under hypoxia, which might be related to the upregulation of Bax and easpase-3 expressions and downregulation of Bcl-xL expression. In addition, β -Elemene deereased effectively the overexpression of HIF-1 α under hypoxia, but the effect eould be downregulated by overexpression of HIF-1α in A549 cells. Conclusion The inereased A549 cells apoptosis under hypoxia condition by β -Elemene might be related to the inhibition of HIF-1 protein expression.

关 键 词：Β-榄香烯 人肺癌细胞 凋亡 HIF-1Α PI-3K/Akt信号转导通路 

分 类 号：R734.2[医药卫生—肿瘤]