PPAR-γ配体吡咯列酮对胆管癌细胞体外侵袭力的影响及其机制  

Effect of PPAR-γ ligand pioglitazone on invasiveness of cholangiocarcinoma cell in vitro and its mechanism

作　　者：李敏[1] 程南生[2] 熊先泽[2] 吴良洪[2] 冉瑞图[2] 

机构地区：[1]四川遂宁市人民医院肝胆外科,四川遂宁629000 [2]四川大学华西医院普外科,四川成都610041

出　　处：《中国现代医学杂志》2007年第16期1962-1965,共4页China Journal of Modern Medicine

基　　金：教育部留学回国人员启动基金资助项目[(2001)345]

摘　　要：目的探讨PPAR-γ配体吡咯列酮(PGZ)对胆管癌细胞体外侵袭力的影响及机制。方法体外培养人肝门胆管癌细胞系QBC939细胞;MTT法检测PGZ对QBC939细胞的增殖抑制率;荧光定量PCR(FQ-PCR)检测PGZ对QBC939细胞侵袭相关基因MMP-7、TIMP-1表达的影响;Matrigel侵袭实验和过河实验检测PGZ对QBC939细胞体外侵袭力的影响。结果MTT提示在24、48和72h干预点,PGZ显著抑制了QBC939细胞的生长(P<0.01);而12h干预点、浓度(5～40μmol/L)时,PGZ的细胞毒性作用不明显(P>0.05)。荧光定量PCR结果显示,PGZ能分别下调和上调MMP-7mRNA、TIMP-1mRNA的表达,但后者无统计学意义(P=0.125)。Matrigel侵袭实验和过河实验显示,随着PGZ浓度的升高,透过Matrigel膜的QBC939细胞数减少、过河时间延长(P<0.01),呈剂量-效应关系。结论PPAR-γ配体PGZ能抑制QBC939细胞的体外侵袭力,其机制可能与下调MMP-7的表达以及抑制QBC939细胞的运动有关。[Objective] To explore the effect of pioglitazone （PGZ）, a ligand of PPAR-γ on invasiveness of cholangiocareinoma cell in vitro and its mechanism. [Methods] Human hilar cholagiocareinoma cell line QBC939 was selected and cultured in vitro. The growth inhibition rate of QBC939 cells was detected by MTT and the influence of pioglitazone on the expression of MMP-7 mRNA and TIMP-1mRNA was examinated using FQ-PCR. At last, the in vitro invasiveness and mobility of QBC939 were quantified by Matrigel invasion assay and crossing-river test respectively. [Results] PGZ can inhibit the growth of QBC939 cells significantly in all experimental groups at 24, 48, 72 hours （P 〈0.01）. Among the low concentration groups （5μmol/1-40μ.mol/1） at the point of 12 hours, the differences of growth inhibition rate were not showed obvious significances （P 〉0.05）. Meanwhile it can down-regulate the expression of MMP-7 mRNA in QBC939 cells （P 〈0.01）, but TIMP-1mRNA was up-regulated without obvious significance （P 〉0.05）. At last, PGZ can significantly reduce cell numbers of QBC939 breaking through matrigel and prolong the crossing-river time （P 〈0.01）. [Conclusion] Pioglitazone, a ligand of PPAR-γ can inhibit the invasiveness of QBC939 cells in vitro via the mechanism which down-regulate the expression of MMP-7 and the mobility of QBC939 cells probably.

关 键 词：胆管癌 PPAR-Γ 吡咯列酮 侵袭力 

分 类 号：R735.8[医药卫生—肿瘤]