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J Cell Mol Med. 2019 May;23(5):3724-3736. doi: 10.1111/jcmm.14280. Epub 2019 Mar 25.

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

Cheng S1, Qian K2,3,4, Wang Y1, Wang G2,3,4, Liu X5, Xiao Y1,2,3,4, Wang X1,6.

Author information

1
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
2
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
3
Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China.
4
Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
5
Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington, District of Columbia.
6
Medical Research Institute, Wuhan University, Wuhan, China.

Abstract

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.

KEYWORDS:

GW9662; PPARγ; bladder cancer; cell cycle; motility

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