4‐nitrophenol exposure in T24 human bladder cancer cells promotes proliferation, motilities, and epithelial‐to‐mesenchymal transition. (17th November 2019) - Dong, Fulu
Abstract : Although health hazards of 4‐nitrophenol (PNP) exposure have been reported, the adverse effects of PNP exposure on cancer biological features are still unknown. We investigated the effects of administration of PNP in T24 human bladder cancer cells. The results showed that PNP exposure promoted cellular proliferation, migration and invasion, inhibited adhesion and apoptosis in vitro . Using quantitative real‐time PCR, we found that (1) the mRNA expression levels of cell‐cycle regulators PCNA, cyclin D1 and COX‐2 were increased in PNP‐treated cells compared to controls, however, that of pro‐apoptotic gene Bax was decreased; (2) the expression level of EMT‐associated gene E‐cadherin was decreased in PNP‐treated cells, whereas those of N‐cadherin, vimentin, snail, and slug were increased; (3) the expression levels of cancer‐promoting genes HIF‐1, IL‐1β, VEGFα and K‐Ras were enhanced, but those of tumor suppressors p53, PTEN and BRCA were decreased. There was a positive association between PNP exposure times and the promotion effects. Finally, we found that the expression level of PPARγ (γ1 isoform) was increased in PNP‐treated T24 cells. GW9662, a specific PPARγ antagonist, attenuated PNP‐induced cell migration and invasion. These findings indicate that PNP exposure may promote bladder cancer growth and progression involving PPARγ signaling. PPARγ is a potential target for development of novel intervention study on environment pollution. Environ. Mol. Mutagen. 61:316–328, 2020. © 2019 Wiley Periodicals, Inc.