Peroxisome proliferator-activated receptor γ (PPARγ), a ligand activated transcription factor, forms a heterodimer with retinoid X receptor α (RXRα), and its transcriptional activity is thought to be maximal in the presence of both PPARγ and RXRα ligands. Though previous studies suggested that thiazolidinediones (TZDs), known as PPARγ ligands, inhibit the growth of certain types of cancer cells, little is known about the growth inhibitory effects mediated though activation of PPARγ/RXRα. We examined the effects of troglitazone (one type of TZDs) and 9-cis retinoic acid, a RXRα ligand, on activation of PPARγ/RXRα and growth inhibition of human pancreatic cancer cell lines (AsPC1, BxPC3, PSN1, PCI6, Panc1, KMP-4, and KMP-7). Combined treatment of troglitazone and 9-cis retinoic acid showed enhanced transcriptional activity and enhanced antiproliferative effects. In PSN1 cells, G1 cell cycle arrest and apoptosis were induced by troglitazone and these effects were enhanced with additional 9-cis RA. Our findings suggest that activation of PPARγ/RXRα pathway might play an important role in growth inhibition of pancreatic cancer cells via G1 cell cycle arrest and apoptosis. This nuclear receptor might be a suitable molecular target for treatment of pancreatic cancers.

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