Sato H, Ishihara S, Kawashima K, Moriyama N, Suetsugu H, Kazumori H, Okuyama T, Rumi M A, Fukuda R, Nagasue N, Kinoshita Y
Second Department of Internal Medicine, Shimane Medical University, Izumo, Shimane, Japan.
Br J Cancer. 2000 Nov;83(10):1394-400. doi: 10.1054/bjoc.2000.1457.
Peroxisome proliferator-activated receptor (PPAR) gamma is expressed in human colon cancer, prostate cancer and breast cancer cells, and PPARgamma activation induces growth inhibition in these cells. PPARgamma expression in human gastric cancer cells, however, has not been fully investigated. We report the PPARgamma expression in human gastric cancer, and the effect of PPARgamma ligands on proliferation of gastric carcinoma cell lines. Immunohistochemistry was used to demonstrate the presence of PPARgamma protein in surgically resected specimens from well differentiated, moderately differentiated and poorly differentiated adenocarcinoma. We used reverse transcription-polymerase chain reaction and Northern and Western blot analyses to demonstrate PPARgamma expression in four human gastric cancer cell lines. PPARgamma agonists (troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J2) showed dose-dependent inhibitory effects on the proliferation of the gastric cancer cells, and their effect was augmented by the simultaneous addition of 9- cis retinoic acid, a ligand of RXRalpha. Flow cytometry demonstrated G1 cell cycle arrest and a significant increase of annexin V-positive cells after treatment with troglitazone. These results suggest that induction of apoptosis together with G1 cell cycle arrest may be one of the mechanisms of the antiproliferative effect of PPARgamma activation in human gastric cancer cells.
过氧化物酶体增殖物激活受体（PPAR）γ在人结肠癌细胞、前列腺癌细胞和乳腺癌细胞中表达，PPARγ激活可诱导这些细胞的生长抑制。然而，PPARγ在人胃癌细胞中的表达尚未得到充分研究。我们报告了PPARγ在人胃癌中的表达以及PPARγ配体对胃癌细胞系增殖的影响。免疫组织化学用于证明PPARγ蛋白在高分化、中分化和低分化腺癌手术切除标本中的存在。我们使用逆转录-聚合酶链反应以及Northern和Western印迹分析来证明PPARγ在四种人胃癌细胞系中的表达。PPARγ激动剂（曲格列酮和15-脱氧-Δ（12,14）-前列腺素J2）对胃癌细胞的增殖显示出剂量依赖性抑制作用，同时添加RXRα配体9-顺式视黄酸可增强其作用。流式细胞术显示用曲格列酮处理后G1期细胞周期停滞以及膜联蛋白V阳性细胞显著增加。这些结果表明，诱导凋亡以及G1期细胞周期停滞可能是人胃癌细胞中PPARγ激活的抗增殖作用机制之一。
