PPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor family of ligand-activated transcription factors and plays an important role in regulating cell proliferation, inflammation and lipid and glucose homeostasis. Our results revealed that PPAR gamma was up-regulated in human bladder cancer (BCa) tissues both at transcriptional and translational levels. Moreover, down-regulation of PPAR gamma mRNA or inhibition of PPAR gamma function (using GW9662, antagonist of PPAR gamma) could significantly suppress the proliferation of BCa cells. Furthermore, the cell cycle arrested in GO/G1 phase was also induced by the down-regulated PPAR gamma possibly through AKT-mediated up-regulation of p21/p27, whereas no significant transformation of apoptosis was observed. In addition, knockdown or inhibition of PPAR gamma might reduce the invasion and migration of BCa cells by affecting epithelial-mesenchymal transition-related proteins through AKT/GSK3 beta signalling pathway. Additionally, in vivo studies showed that BCa cell proliferation was significantly suppressed by GW9662. In conclusion, our results indicated that PPAR gamma might be crucial for BCa tumorigenesis by interfering with the motility and viability of BCa cells.