文章摘要
崔 畅,龚颖芸,肖正睿,戴启盈,冷 静.PI3K-AKT信号通路对人肝癌Huh-7细胞乳酸和乙酰化修饰水平及细胞生长的影响[J].南京医科大学学报,2014,(5):557~562
PI3K-AKT信号通路对人肝癌Huh-7细胞乳酸和乙酰化修饰水平及细胞生长的影响
Depression of acetylation by PI3K-Akt inhibitors reverses glycolytic phenotype and cellular proliferation in Huh-7 cells
投稿时间:2013-08-13  
DOI:10.7655/NYDXBNS20140505
中文关键词: PI3K/Akt  mTOR  肝细胞癌  糖酵解  乙酰化
英文关键词: PI3K/Akt  mTOR  hepatic carcinoma  aerobic glycolysis  acetylation
基金项目:大学生创新创业训练计划重点项目(2012JSS PITP1008)
作者单位
崔 畅 南京医科大学第一临床医学院,江苏 南京 210029 
龚颖芸 南京医科大学第一临床医学院,江苏 南京 210029 
肖正睿 南京医科大学第一临床医学院,江苏 南京 210029 
戴启盈 南京医科大学第一临床医学院,江苏 南京 210029 
冷 静 南京医科大学病理系,江苏 南京 210029 
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中文摘要:
      目的:探讨PI3K/Akt信号通路对人肝细胞癌Huh-7细胞乙酰化及糖酵解的影响及机制?方法:体外培养Huh-7细胞株,应用不同浓度的PI3K/Akt抑制剂LY294002与mTOR抑制剂雷帕霉素分别进行干预;乳酸试剂盒法检测乳酸水平;Western blot法检测肿瘤细胞中三磷酸腺苷柠檬酸盐裂解酶(adenosine triphosphate-citrate lyase,ACL)表达水平与乙酰化修饰水平;WST法检测细胞增殖水平?结果:①LY294002干预组的乳酸水平低于DMSO对照组,下降66.15%,细胞内ACL的表达水平下降20.84%,乙酰化水平在多位点表达水平下降(P < 0.01,n = 3);②雷帕霉素干预组的乳酸水平低于DMSO对照组,下降90.16%,细胞内ACL的表达水平下降64.16%,乙酰化水平在多个位点表现出不同水平的下降(P < 0.01,n = 3);③以DMSO干预作为对照,20 mmol/L的LY294002和20 μg/L的雷帕霉素分别作用24 h后,对Huh-7细胞的增殖抑制率分别为24.78%和20.67%(P < 0.01,n = 3)?结论:Huh-7细胞中活化的PI3K/Akt/mTOR信号通路能通过提高ACL的表达,上调细胞内乙酰化的修饰水平,从而增加肿瘤细胞的糖酵解,促进肿瘤细胞的生长?
英文摘要:
      Objective:To explore the role of PI3K/Akt signal pathway in acetylation and aerobic glycolysis in Huh-7 cells. Methods:We treated Huh-7 cells with LY294002 (PI3K/Akt inhibitor) and rapamycin (mTOR inhibitor). DMSO treatment was set as negative control. Lactate concentrations were measured by lactate kits. The expression of ACL and acetylation was measured by Western blots. Cell viability was determined by WST assay. Results:①Under LY294002,lactate concentrations decreased by 66.15%. Expression levels of ACL declined by 20.84%. Acetylation levels decreased at several sites(P < 0.01,n = 3). ②Under rapamycin,lactate concentrations decreased significantly by 90.16%. Expression levels of ACL declined by 64.16%. Acetylation levels were down-regulated variously at different sites (P < 0.01,n =3 ). ③After 24 h culture with 20mmol/L LY294002 or 20 μg/L rapamycin,the cell growth inhibition ratio reached to 24.78% and 20.67%,respectively(P < 0.01,n = 3). Conclusion:PI3K/Akt/mTOR signal pathway promotes the aerobic glycolysis of cancer cells by up-regulating the expression of ACL genes and the levels of acetylation,which may contribute to the tumor growth.
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