PPARγ expression in esophageal cancer and effect of PPARγ ligand

研究了过氧化物酶体增殖物激活受体(PPAR) γ在人食管鳞状细胞癌中的表达及PPARγ配体对食管癌细胞生长的影响。逆转录聚合酶链反应和Western blot分析显示，人食管癌细胞株KE-5、KE-8和KE-10均表达PPARγ mRNA和蛋白。PPARγ配体曲格列酮处理后，这些细胞的生长呈剂量依赖性。流式细胞术分析显示，曲格列酮治疗后G1细胞周期阻滞，Ki-67染色阳性率明显降低。这些结果提示PPARγ配体在食管癌中的抗增殖作用部分是由对细胞周期的负作用诱导的。Involucrin在鳞状上皮细胞中表达，被用作鳞状细胞终末分化的标准标记物。曲格列酮诱导食管癌细胞中天花素表达增加，表明PPARγ配体增强了食管癌细胞的分化。进一步，我们检测了PPARγ配体是否诱导了这些细胞的凋亡。曲格列酮治疗后未观察到DNA断裂，说明细胞凋亡不参与PPARγ配体在食管癌中的抗增殖作用。最后，我们在体内检测了曲格列酮对肿瘤生长的影响。我们观察到治疗组和未治疗组的肿瘤生长无差异。

We investigated the expression of peroxisome proliferator-activated receptor (PPAR) γ in human esophageal squamous cell carcinomas and the effect of PPARγ ligand on cell growth in esophageal cancer. Reverse transcription-polymerase chain reaction and Western blot analysis showed that human esophageal cancer cell lines, KE-5, KE-8 and KE-10, expressed PPARγ mRNA and protein. Cell growth of these cells were inhibited after treatment with PPARγ ligand, troglitazone, in a dose-dependent manner. Flow cytometric analysis demonstrated G1 cell cycle arrest and positive rate of Ki-67 staining was significantly decreased after troglitazone treatment. These results suggested that antiproliferative effect of PPARγ ligand in esophageal cancer is in part induced by negative effect on the cell cycle. Involucrin is expressed in squamous epithelial cells and has been used as a standard marker of terminal differentiation of squamous cells. Troglitazone treatment induced increased expression of involucrin in esophageal cancer cells, indicating that PPARγ ligand augmented cell differentiation in esophageal cancer cells. Furthermore, we examined whether PPARγ ligand induced apoptosis in these cells or not. There was no DNA fragmentation observed after troglitazone treatment, meaning that apoptosis was not involved in antiproliferative effect of PPARγ ligand in esophageal cancer. Finally, we examined the effect of troglitazone on tumor growth in vivo. We observed no difference in tumor growth between treated and untreated group.