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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
【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.
【Key words】 SIRT1; HepG2; Hepatocellular carcinoma; Proliferation 2634;
- 【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