PPAR? inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells.

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR?) 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? was up-regulated in human bladder cancer (BCa) tissues both at transcriptional and translational levels. Moreover, down-regulation of PPAR? mRNA or inhibition of PPAR? function (using GW9662, antagonist of PPAR?) could significantly suppress the proliferation of BCa cells. Furthermore, the cell cycle arrested in G0/G1 phase was also induced by the down-regulated PPAR? possibly through AKT-mediated up-regulation of p21/p27, whereas no significant transformation of apoptosis was observed. In addition, knockdown or inhibition of PPAR? might reduce the invasion and migration of BCa cells by affecting epithelial-mesenchymal transition-related proteins through AKT/GSK3? signalling pathway. Additionally, in vivo studies showed that BCa cell proliferation was significantly suppressed by GW9662. In conclusion, our results indicated that PPAR? might be crucial for BCa tumorigenesis by interfering with the motility and viability of BCa cells.

SUBMITTER: Cheng S 

PROVIDER: S-EPMC6484405 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature