PPARγ参与调节胃癌MKN45细胞株VEGF mRNA的表达及临床意义

Involvement of PPARγ in regulation of the expression of VEGF mRNA in gastric cancer cell line MKN45 and clinical significance

目的研究过氧化物酶体增殖激活受体(PPARγ)是否体外参与调节胃癌MKN45细胞VEGF mRNA的表达及临床意义。方法体外培养人胃癌细胞系MKN45,不同浓度的PPARγ激动剂(曲格列酮),PPARγ特异性抑制物体外作用细胞,EMSA测定细胞PPARγ的活性,RT-PCR检测细胞VEGF mRNA的表达。结果相对于对照组,随曲格列酮浓度的增加,胃癌MKN45细胞株PPARγ活性显著性升高(P<0.01),VEGF mRNA的表达显著性降低(P<0.01),且呈剂量依赖关系;PPARγ特异性抑制物能显著性抑制曲格列酮诱导的胃癌MKN45细胞株PPARγ的活化和VEGF mRNA的表达的下调(P<0.01)。结论PPARγ可能参与调节胃癌MKN45细胞株VEGF mRNA的表达,曲格列酮通过激活PPARγ,抑制胃癌MKN45细胞株VEGF mRNA的表达,可能为胃癌的治疗提供新的靶点。

Objective To investigate whether PPARγ is involved in regulation of the expression of VEGF mRNA in gastric cancer cell line MKN45 and the clinical significance. Methods Human gastric cancer cell line MKN45 was cultured and treated with different concentrations of PPARγ agonist （Troglitazone） and PPARγ inhibitor in vitro. The activity of PPARγ was measured by using electrophoretic mobility shift assay. The expression of VEGF mRNA was detected by using RT-PCR. Results As compared with control group, Troglitazone induced a concentration- dependent increase of PPARγ activity and a decrease in the expression of VEGF mRNA in gastric cancer cell line MKN45. Ra-parnycin could obviously inhibit the activation of PPARγ and the down-regulation of the VEGF mRNA expression induced by Troglitazone（P〈0.01）. Conclusion PPARγ is likely involved in regulation of the expression of VEGF mRNA in gastric cancer cell line MKN45. Troglitazone could activate PPARγ and induce a decrease in the expression of VEGF mRNA in MKN45 gastric cells. PPARγ may become a new target of treatment of gastric cancer.