吡格列酮对胃癌细胞生长的影响及其机制的研究

Expression of peroxisome proliferator-activated receptor γ in human gastric carcinoma cell and inhibitory effects of pioglitazone

目的 :研究过氧化物酶增殖因子活化受体γ(PPARγ)在人胃癌细胞株MKN 45的表达 ;观察PPARγ激活剂吡格列酮对胃癌细胞生长的影响以及是否引起凋亡基因c myc表达的变化 ,探讨其作用机制。方法 :采用RT PCR法检测PPARγ的表达 ,以不同浓度的吡格列酮干预细胞的生长 ,四甲基偶氮唑盐比色法检测吡格列酮激活剂对胃癌细胞株增殖活性的效应 ,RT PCR法检测药物干预前后c myc基因表达的变化。结果 :PPARγ在胃癌细胞株MKN 45中有表达。 0 .0 1μmol·L- 1 吡格列酮对MKN 45细胞的增殖无明显影响 ;1μmol·L- 1 吡格列酮作用 48h则明显降低MKN 45细胞的存活率 ,与不加吡格列酮的对照组比较有显著差异 (P <0 .0 5 ) ,随着药物浓度增加和培养时间延长 ,这一作用愈加明显。随着药物浓度的增加 ,c myc基因的表达呈下降趋势。结论 :PPARγ在胃癌细胞株MKN 45中有表达 ,PPARγ激活剂吡格列酮抑制胃癌细胞的生长 ,且引起c myc基因表达的下调 。

Objective To study the peroxisome proliferators-activated receptor(PPAR)γ expression in human gastric cancer MKN?45 cells and the effect of PPARγ ligand on proliferation of gastric carcinoma cell line and on the changes of c-myc gene expression.Methods Reverse transcripition-polymerase chain reaction was used to demonstrate PPARγ expression in MKN?45 cell line.PPARγ agonist(pioglitazone) showed dose-dependent inhibitory effects on the proliferation of the gastric cancer cells.Pioglitazone also reduced c-myc gene expression in MKN?45 cells.Results Peroxisome proliferators activated receptor(PPAR)γ was expressed in MKN?45 cells. 0.01?μmol·L -1 pioglitazone had no effect on proliferation of MKN?45 cells. MKN?45 cells cultured by 1?μmol·L -1 pioglitazone for 48 hours showed inhibitory effect and c-myc gene demonstrated a significant decrease.Conclusion These results suggest PPARγ agonist(pioglitazone) can inhibit proliferation of gastric carcinoma cell line.And the reduction of c-myc gene expression can be one of the mechanisms of the antiproliferative effect of PPARγ activation in human gastric cancer cells.