Sirt1促进肝癌细胞增殖和侵袭活性的分子机制

Oncogene Slit1 Facilitates Proliferation and Invasion of Hepatocellular Carcinoma Cell

目的:探讨Sirt1基因在肝癌组织和癌旁组织中表达差异,进一步检测其对肝癌细胞增殖和侵袭活性的调控。方法:收集30例肝癌手术患者的病变组织和癌旁组织,通过Real time-PCR检测Sirt1基因的表达差异,并对其中6例组织通过western blot验证。在转染Sirt1基因或干扰掉该基因后,采用MTT的方法检测HepG2细胞的增殖活性,通过Transwell小室的方法检测HepG2细胞的侵袭活性。结果:Real time-PCR检测发现Sirt1 mRNA在肝癌组织中高表达,同样,Western blot检测也发现Sirt1在肝癌组织中高表达,而在癌旁组织中表达较低。过表达Sirt1导致HepG2细胞过度增殖,侵袭能力增加;相反,敲除该基因,细胞增殖和侵袭活性被抑制。结论:Sirt1在肝癌组织中高表达并且介导肝癌细胞增殖和侵袭活性。该基因在肝癌组织中的过量表达有助于肝癌的临床诊断,同时Sirt1在肝癌的恶性肿瘤生物活性中发挥着重要的作用,因此,Sirt1是一个潜在的治疗肝癌的药物作用靶点,为开发新的抗肿瘤药物提供了新的治疗靶点。

Objective： To investigate the expression profile of Sirtl mRNA in hepatocellular carcinoma samples, the final goal of this study is to clarify the role of Sirtl in hepatocellular carcinoma cells＇ proliferation and invasion. Mothods： Real time-PCR and Western blot were used to determine the expression of Sirtl expression in mRNA or protein levels. MTT assay and Transwell assay were performed to investigate overexpression or depletion of Sirtl on HepG2 cells＇ proliferation and invasion. Result： Sirtl overexpressed in hepatocellular carcinoma samples. Moreover, overexpression of Slitl enhances HepG2 cell proliferation and invasion, however, knocking down Slit2 resultes in reduce of proliferation and invasion. Conclusion： Slitl play an important role in regulations of hepatocellular carcinoma＇s proliferation and invasion. The elevated Sirtl expression in hepatocellular carcinoma tissue will facilitate clinical diagnosis and imply that this is a potential target for hepathocellular carcinoma therapy.