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沉默信息调节因子1促进肝细胞增殖的机制

Mechanism of SIRT1 promoting the proliferation of hepatocytes

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【作者】 刘灏李川江王汉宁刘正军

【Author】 LIU Hao;LI Chuan-jiang;WANG Han-ning;LIU Zheng-jun;Department of Vascular Surgery,Nanfang Hospital Southern Medical University;

【机构】 南方医科大学南方医院1血管外科南方医科大学南方医院肝胆外科广东省第二人民医院普外科

【摘要】 目的:明确沉默信息调节因子1(SIRT1)对肝癌细胞系HepG2细胞生物学功能的影响。方法:构建pCDNA4-SIRT1质粒,合成SIRT1的siRNA,转染肝癌HepG2细胞系。XTT法及CCK-8法检测细胞的增殖活力、流式细胞仪检测细胞周期及细胞凋亡率、Western blot检测蛋白的表达。结果:干扰SIRT1表达均可明显抑制HepG2细胞增殖(P<0.001);干扰SIRT1表达均可明显抑制HepG2细胞S期(P<0.01),而使G1期明显增加(P<0.001);干扰SIRT1表达可明显促进HepG2细胞凋亡(P<0.001);在HepG2细胞中当抑制SIRT1表达时,PTEN的乙酰化水平、磷酸化AKT和PI3K的表达水平明显增加。结论:SIRT1在肝癌细胞系HepG2增殖中起重要作用,同时存在抑制其凋亡的作用,该作用涉及PTEN/PI3K/AKT信号转导通路。

【Abstract】 Objective To investigate the effects of SIRT1 on the biological behaviors of liver cancer cell lines HepG2.Methods pCDNA4-SIRT1 plasmid was constructed,and siRNA of SIRT1 was synthesized and transfected into HepG2 cells.The proliferation of HepG2 cells was evaluated by XTT assay and CCK-8 kit;flow cytometry was employed to analyze the distribution of cell cycle and apoptosis rate;and Western blotting was performed to detect the expression of PTEN,PI3K and AKT.Results Down-regulation of SIRT1 could significantly suppress the proliferation of HepG2 cells(P < 0.001),could decrease the percentage of HepG2 cells in S and G2 / M phase(P < 0.01) while increase the percentage of HepG2 cells in G0 / G1 phase(P < 0.001),could inhibit the apoptosis of HepG2 cells(P < 0.001),and could up-regulate the expressions of PTEN,PI3K and AKT.Conclusion SIRT1 played a significant role in the proliferation and apoptosis of HepG2 cells,which was correlated with PTEN / PI3K / AKT signaling pathway.

【关键词】 SIRT1HepG2肝细胞癌增殖
【Key words】 SIRT1HepG2Hepatocellular carcinomaProliferation 2634
【基金】 国家自然科学基金面上项目(编号:81172383);广东省自然科学基金资助博士启动项目(编号:S2011040002946)
  • 【文献出处】 实用医学杂志 ,The Journal of Practical Medicine , 编辑部邮箱 ,2013年16期
  • 【分类号】R735.7
  • 【被引频次】2
  • 【下载频次】111
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