沉默信息调节因子1对胃癌侵袭的影响及其机理研究

目的 研究沉默信息调节因子1 （SIRT1）蛋白在胃癌组织中的表达及其对胃癌侵袭的影响和可能机理。方法 采用免疫组化SP法检测46例胃癌组织中SIRT1和血管内皮生长因子A （VEGF-A）蛋白的表达；采用Kaplan-Meier法分析SIRT1蛋白和VEGF-A蛋白表达对胃癌患者预后的影响；采用Western blot法检测GES-1人胃黏膜细胞株及SGC7901人胃癌细胞株中SIRT1蛋白和VEGF-A蛋白的表达；采用siRNA小干扰技术特异性干扰SGC7901细胞株中SIRT1基因的表达后，检测SIRT1蛋白和VEGF-A蛋白的表达；通过细胞侵袭实验检测不同处理后SGC7901细胞侵袭能力的变化。结果 与正常胃黏膜组织比较，胃癌组织中SIRT1蛋白和VEGF-A蛋白均呈高表达（P＜0.050）。SIRT1蛋白阳性表达患者的生存情况较差（P=0.001），SIRT1及VEGF-A蛋白均呈阳性表达者的生存情况较差（P=0.006），但VEGF-A蛋白表达与胃癌患者的预后无关（P=0.091）。SGC7901细胞中SIRT1蛋白（P=0.010） 和VEGF-A蛋白（P=0.020） 的表达较GES-1细胞上调。构建SIRT1-siRNA特异性抑制SIRT1基因的表达后（siRNA阳性组），SIRT1蛋白和VGEF-A蛋白的表达均下调（P=0.010），且SGC7901细胞的侵袭能力下降（P=0.000）。结论 SIRT1基因可能通过促进VEGF-A蛋白的表达而促进胃癌的侵袭，其可能是抑制胃癌侵袭的一个治疗靶点。

Effect and Mechanism of Sirtuin 1 in Invasion of Gastric Cancer

Objective To investigate the effect and mechanism of silent information regulator 1 （SIRT1）in invasion of human gastric cancer. Methods The expressions of SIRT1 protein and vascular endothelial growth factor A（VEGF-A） protein in 46 cases of gastric cancer were tested by immunohistochemical SP method;the effect of expressions of SRIT1 and VEGF-A protein on prognosis of gastric cancer was analyzed by Kaplan-Meier test;the expressions of SRIT1 and VEGF-A protein in human gastric mucosa GES-1 cells and SGC7901 cells were tested by Western blot method;after the interference of siRNA on SIRT1 gene, expressions of SRIT1 and VEGF-A protein were also tested by Western method, and the invasion ability was determined by Transwell test. Results Compared with normal gastric mucosa tissues, expression levels of SIRT1 and VEGF-A protein of gastric tissues were both higher （P〈0.050）, and survival situation of patients with SIRT1-positive （P=0.001） or SIRT1-positive and VEGF-A-positive （P=0.006） were both bad, but there was no significant difference on the relationship between prognosis of gastric cancer and expression of VEGF-A protein （P=0.091）. Expression levels of SITR1 protein （P=0.010） and VEGF-A protein （P=0.020） in GES-1 cells were both higher than those of SGC7901 cells. In siRNA positive group, expressions of SIRT1 and VEGF-A protein （P=0.010） of SGC7901 cells down-regulated, and invasion ability decreased （P=0.000）. Conclusion SIRT1 gene may promote the expression of VEGF-A protein and the invasion ability of gastric cancer, it may be a therapeutic target of invasion inhibition for gastric cancer.