Open AccessPPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells
Author(s) -
Cheng Songtao,
Qian Kaiyu,
Wang Yejinpeng,
Wang Gang,
Liu Xuefeng,
Xiao Yu,
Wang Xinghuan
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14280
Subject(s) - cell growth , peroxisome proliferator activated receptor , microbiology and biotechnology , cell cycle , nuclear receptor , gene knockdown , motility , carcinogenesis , protein kinase b , pi3k/akt/mtor pathway , biology , cell migration , apoptosis , cancer cell , peroxisome proliferator activated receptor delta , transcription factor , cell , receptor , cancer research , signal transduction , cancer , biochemistry , genetics , gene
Peroxisome proliferator‐activated receptor gamma (PPARγ) 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 PPARγ was up‐regulated in human bladder cancer (BCa) tissues both at transcriptional and translational levels. Moreover, down‐regulation of PPARγ mRNA or inhibition of PPARγ function (using GW9662, antagonist of PPARγ) could significantly suppress the proliferation of BCa cells. Furthermore, the cell cycle arrested in G0/G1 phase was also induced by the down‐regulated PPARγ possibly through AKT‐mediated up‐regulation of p21/p27, whereas no significant transformation of apoptosis was observed. In addition, knockdown or inhibition of PPARγ might reduce the invasion and migration of BCa cells by affecting epithelial‐mesenchymal transition‐related proteins through AKT/GSK3β signalling pathway. Additionally, in vivo studies showed that BCa cell proliferation was significantly suppressed by GW9662. In conclusion, our results indicated that PPARγ might be crucial for BCa tumorigenesis by interfering with the motility and viability of BCa cells.