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Silent information regulator 1 gene induces aging of hepatocellular carcinoma cells via p53/p21 pathway
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- Author:
- No author available
- Journal Title:
- Acta Academiae Medicinae Militaris Tertiae
- Issue:
- 19
- DOI:
- No doi available
- Key Word:
- 沉默信息调节因子1;肝细胞癌;肿瘤细胞系;细胞衰老
Abstract： 目的 探讨慢病毒介导的沉默信息调节因子1(silent information regulator1,SIRT1)基因沉默对肝癌细胞老化的影响及机制.方法 通过慢病毒介导的shRNA干扰技术靶向沉默SIRT1的表达,并通过Real-time PCR和Westernblot验证SIRT1基因的沉默效果.BrdU标记实验检测细胞增殖情况,流式细胞仪检测细胞周期变化；β-半乳糖苷酶染色观察肝癌细胞有无老化；Western blot检测衰老相关基因p53和p21蛋白的变化.结果 慢病毒介导的shRNA能显著抑制细胞SIRT1的mRNA及蛋白水平.SIRT1沉默能抑制肝癌细胞的增殖,抑制率达70％ ～ 80％;同时,SIRT1沉默能显著诱导G1期细胞周期阻滞:感染shCont的细胞处于G1期比例为(44.29±0.36)％,而感染shSIRTl-1的细胞处于G1期细胞为(69.20±1.24)％,感染shSIRTl-2的细胞处于G1期比例为(65.86±1.75)％.SIRT1沉默后肝癌细胞中衰老相关的β-半乳糖苷酶染色显著增高,阳性细胞占40％ ～50％ (P＜0.05),并伴随衰老相关基因p53和p21蛋白表达增加.结论 SIRT1基因沉默可能通过p53/p21途径促进细胞衰老.
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