PPARγ expression in esophageal cancer and effect of PPARγ ligand

我们研究了过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，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（RT-PCR）和Western blot分析显示，人食管癌细胞系KE-5、KE-8和KE-10均表达PPARγ mRNA和蛋白。经PPARγ配体曲格列酮处理后，这些细胞的生长受到抑制，呈剂量依赖性。流式细胞仪分析显示曲格列酮处理后细胞周期阻滞于G1期，Ki-67阳性率明显降低。结果提示，PPARγ配体的抗食管癌增殖作用部分是通过抑制细胞周期而实现的。包被蛋白在鳞状上皮细胞中表达，并已被用作鳞状细胞终末分化的标准标志物。曲格列酮处理诱导食管癌细胞中外皮蛋白表达增加，表明PPARγ配体增强食管癌细胞的细胞分化。此外，我们还检测了PPARγ配体是否诱导这些细胞凋亡。曲格列酮治疗后未观察到DNA断裂，这意味着细胞凋亡不参与PPARγ配体在食管癌中的抗增殖作用。最后，我们研究了曲格列酮对体内肿瘤生长的影响。我们观察到治疗组和未治疗组之间的肿瘤生长没有差异。

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.