Expression of peroxisome proliferator-activated receptor (PPAR)γ in gastric cancer and inhibitory effects of PPARγ agonists

Peroxisome proliferator-activated receptor (PPAR) gamma is expressed in human colon cancer, prostate cancer and breast cancer cells, and PPAR gamma activation induces growth inhibition in these cells. PPAR gamma expression in human gastric cancer cells, however, has not been fully investigated. We report the PPAR gamma expression in human gastric cancer, and the effect of PPAR gamma ligands on proliferation of gastric carcinoma cell lines. Immunohistochemistry was used to demonstrate the presence of PPAR gamma 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 PPAR gamma expression in four human gastric cancer cell lines. PPAR gamma 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 RXR alpha. 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 PPAR gamma activation in human gastric cancer cells. (C) 2000 Cancer Research Campaign.