International Journal of Medical Sciences

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23 October 2018

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Int J Med Sci 2018; 15(3):228-237. doi:10.7150/ijms.22408

Research Paper

Pioglitazone Use and Risk of Bladder Cancer: an In Vitro Study

Shao-ling Yang1,2*, Ji-jiao Wang1,3*, Ming Chen1,4, Lu Xu1, Nan Li1, Yi-li Luo1, Le Bu1, Man-na Zhang1, Hong Li1✉, Ben-li Su3✉

1. Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China;
2. Soochow University School of Medicine, Suzhou, 215000, China;
3. Department of Endocrinology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China;
4. Nanjing Medical University, Nanjing, 210000, China;
*Contributed equally

Abstract

Aims: Whether pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma agonist, increases the risk of developing bladder cancer has been debated for several years. The aim of this study was to investigate the in vitro effects of PIO on normal urothelial transitional epithelium (NUTE) cells and bladder cancer (J82) cells to further evaluate the risk.

Methods: NUTE cells were obtained from Sprague-Dawley rats. NUTE and J82 cells were treated with different concentrations of PIO for various time periods. Cell proliferation was tested by the MTT assay. Cell apoptosis was evaluated by flow cytometry. The expressions of p53, cyclin D1, Bcl-2, and Bax were determined by qRT-PCR and western blots.

Results: After 24 hours, the treatment of NUTE cells with 10 μmol/L PIO led to morphological changes, without changes in J82 cells. Moreover, PIO inhibited the proliferation and induced apoptosis of NUTE cells, but not J82 cells, in a time- and dose-dependent manner. However, PIO did not alter the growth of cells from other tissues. In addition, treatment with PIO for up to 72 hours did not result in changes in the expressions of p53, cyclin D1, Bcl-2, and Bax in NUTE cells and J82 cells. Interestingly, PIO significantly downregulated the protein levels of p53 and cyclin D1 in J82 cells, but not NUTE cells after more than 192 hours of treatment.

Conclusions: PIO did not promote malignant alterations of NUTE cells or stimulate proliferation of J82 cells. PIO decreased the expression of p53 and cyclin D1 in J82 cells after long-term culture, which suggested that PIO may be helpful for diabetic patients with bladder cancer.

Keywords: PPAR gamma, pioglitazone, bladder cancer

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How to cite this article:
Yang Sl, Wang Jj, Chen M, Xu L, Li N, Luo Yl, Bu L, Zhang Mn, Li H, Su Bl. Pioglitazone Use and Risk of Bladder Cancer: an In Vitro Study. Int J Med Sci 2018; 15(3):228-237. doi:10.7150/ijms.22408. Available from http://www.medsci.org/v15p0228.htm