Peroxisome proliferator-activated receptor (PPAR) γ is expressed in human colon cancer, prostate cancer and breast cancer cells, and PPARγ activation induces growth inhibition in these cells. PPARγ expression in human gastric cancer cells, however, has not been fully investigated. We report the PPARγ expression in human gastric cancer, and the effect of PPARγ ligands on proliferation of gastric carcinoma cell lines. Immunohistochemistry was used to demonstrate the presence of PPARγ 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 PPARγ expression in four human gastric cancer cell lines. PPARγ agonists (troglitazone and 15-deoxy-Δ12,14-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 RXRα. 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 PPARγ activation in human gastric cancer cells. © 2000 Cancer ResearchCampaign

Summary Peroxisome proliferator-activated receptor γ (PPARγ) ligands have been implicated in the growth inhibition and differentiation of certain human cancers with diverse tissue origin. In this study, expression of PPARγ in human hepatocellular carcinoma (HCC) and the effect of PPARγ ligands on HCC cells were investigated in vitro using Hep G2, HuH-7, KYN-1 and KYN-2 cell lines. All cell lines were found to express functionally active PPARγ and a marked growth inhibition was induced by thiazolidinedione ligands troglitazone, and pioglitazone as well as with its natural ligand 15-deoxy-∆ 12,14 -prostaglandin J 2 . The growth inhibitory effect was associated with a dose-dependent inhibition of DNA synthesis, cell cycle progression and α fetoprotein expression.

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