罗格列酮抑制胰腺癌细胞侵袭和转移的机制  

The mechanism of inhibiting the invasion and metastasis of pancreatic cancer cells by rosiglitazone

作　　者：王闯[1] 周晓华[2] 曾宪成[1] 黄延年[1] 薛平[3] 

机构地区：[1]广州市增城区人民医院(中山大学附属博济医院)普通外科,511300 [2]广州医科大学附属第二医院超声科,510260 [3]广州医科大学附属第二医院肝胆外科,510260

出　　处：《中华实验外科杂志》2017年第3期378-380,共3页Chinese Journal of Experimental Surgery

基　　金：广东省自然科学基金,广州市科技计划项目,广州市卫生局项目（20141A011117、20151A011112）

摘　　要：目的 观察胰腺癌细胞是否存在过氧化物酶体增殖剂激活受体γ（PPARγ）/第10 号染色体上缺失与张力蛋白同源的磷酸酯酶基因（PTEN）/基质金属蛋白-9（MMP-9）信号通路,以及基因PTEN和MMP-9 的变化,探讨罗格列酮对胰腺癌细胞侵袭和转移的机制.方法 培养人胰腺导管上皮癌细胞（PANC-1）,经40μmol/L PPARγ配体罗格列酮和10μmol/L抑制剂GW9662 处理24h后,用细胞的活力测定[四唑氮化合物（MTS）法]测胰腺癌细胞活力,用伤口愈合实验和基质胶（Matrigel）体外侵袭实验检测细胞的迁移能力,用反转录-聚合酶链反应（RT-PCR）检测细胞PTEN 和MMP-9 mRNA的相对表达.结果 罗格列酮对PANC-1胰腺癌细胞的增殖具有抑制作用,且呈剂量依赖性,明显抑制胰腺癌细胞侵袭和转移,增加（2.51±0.05）倍PTEN mRNA,减少（0.39±0.02）倍MMP-9 mRNA;而GW9662无此作用.结论 胰腺癌细胞可能存在PPARγ/PTEN/MMP-9信号通路,通过上调PTEN和下调MMP-9的表达,来抑制胰腺癌细胞的侵袭和转移.Objective To investigate whether peroxisome proliferator-activated receptor- γ （PPARγ）/phosphatase and tensin homolog deleted on chromosome ten （PTEN）/matrix metalloprotein-9 （MMP-9） signaling pathway in pancreatic cancer cells, and PTEN and MMP-9 changes, to further clarify the mechanism of inhibiting the invasion and metastasis of pancreatic cancer cells by rosiglitazone.Methods Cultured human pancreatic ductal epithelial cancer cells （PANC-1）.After 40 μmol/L PPARγ ligand rosiglitazone and 10μmol/L inhibitor GW9662 treated for 24 h, measuring the viability of liver cancer cell measured by 3-（4,5-Dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium （MTS） method, the migration ability measured by wound healing assay and Matrigel method, PTEN and MMP-9 expressions of PANC-1 cells treated with Rosiglitazone and GW9662, were determined by reverse transcriptase polymerase chain reaction （RT-PCR）.ResultsRosiglitazone inhibited the proliferation of PANC-1 pancreatic cancer cells in a dose-dependent manner, inhibited the invasion and metastasis of pancreatic cancer cells, increased （2.51±0.05） times PTEN mRNA, and decreased （0.39±0.02） times MMP-9 mRNA, whereas GW9662 had no effect.Conclusion PPARγ/PTEN/MMP-9 signaling pathway may exist in pancreatic carcinoma, through the up-regulation of PTEN and down-regulation of MMP-9 expression, to inhibit invasion and metastasis of cancer cells.

关 键 词：过氧化物酶体增殖物激活受体 胰腺癌细胞 第10号染色体上缺失与张力蛋白同源的磷酸酯酶基因 肿瘤转移 

分 类 号：R735.9[医药卫生—肿瘤]