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

Peroxisome proliferator-activated receptor (PPAR) gamma is expressed in hum an colon cancer, prostate cancer and breast cancer cells, and PPAR gamma ac tivation induces growth inhibition in these cells. PPAR gamma expression in human gastric cancer cells, however, has not been fully investigated. We r eport the PPAR gamma expression in human gastric cancer, and the effect of PPAR gamma ligands on proliferation of gastric carcinoma cell lines. Immuno histochemistry was used to demonstrate the presence of PPAR gamma protein i n surgically resected specimens from well differentiated, moderately differ entiated and poorly differentiated adenocarcinoma. We used reverse transcri ption-polymerase chain reaction and Northern and Western blot analyses to d emonstrate PPAR gamma expression in four human gastric cancer cell lines. P PAR gamma agonists (troglitazone and 15-deoxy-Delta (12,14)-prostaglandin J 2) showed dose-dependent inhibitory effects on the proliferation of the gas tric cancer cells, and their effect was augmented by the simultaneous addit ion of 9-cis retinoic acid, a ligand of RXR alpha. Flow cytometry demonstra ted G1 cell cycle arrest and a significant increase of annexin V-positive c ells after treatment with troglitazone. These results suggest that inductio n of apoptosis together with G1 cell cycle arrest may be one of the mechani sms of the antiproliferative effect of PPAR gamma activation in human gastr ic cancer cells. (C) 2000 Cancer Research Campaign.