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Pioglitazone Suppresses Urothelial Tumorigenesis In Vitro: A Potential Chemopreventive Agent
Nguyen Thu Quynh1, Yujiro Nagata2, Takuo Matsukawa1
1Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Background/Aim:
Pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma agonist, is typically used to treat type 2 diabetes mellitus. In addition to its metabolic effects, PIO exhibits various biological activities, including potential anticancer effects. However, its efficacy and mechanistic relevance in the development and progression of cancer, including urothelial carcinoma, remain unclear. Herein, we investigated the functional impact of PIO on urothelial tumorigenesis.
Materials And Methods:
An in vitro urothelial neoplastic transformation model was established by inducing SV-HUC-1 cells with a chemical carcinogen 3-methylcholanthrene. This model was used to investigate the effects of PIO on neoplastic/malignant transformation.
Results:
PIO significantly inhibited the neoplastic/malignant transformation of SV-HUC-1 cells. Moreover, PIO treatment up-regulated tumor suppressors, including p53 and phosphatase and tensin homolog (PTEN), as well as the epithelial marker E-cadherin, while down-regulating the mesenchymal marker N-cadherin and the oncogenic factor nuclear factor kappa B (NF-κB), as confirmed by protein and mRNA expression analyses.
Conclusion:
PIO has a chemopreventive effect on urothelial tumorigenesis, supporting its potential use as a preferred anti-diabetic agent for patients with a risk or history of urothelial carcinoma.
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