4-nitrophenol exposure in T24 human bladder cancer cells promotes proliferation, motilities, and epithelial-to-mesenchymal transition
4-nitrophenol exposure in T24 human bladder cancer cells promotes proliferation, motilities, and epithelial-to-mesenchymal transition
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DOI：
10.1002/em.22345
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发表时间：
2020-03-01
影响因子：
2.8
通讯作者：
Zhang, Yonghui
中科院分区：
文献类型：
--
作者：
Dong, Fulu;Chen, Lu;Zhang, Yonghui
虽然有报道称接触4-硝基苯酚（PNP）会对健康造成危害，但接触PNP对癌症生物学特征的不良影响仍不清楚。我们研究了PNP在T24人膀胱癌细胞中的施用效果。结果表明，PNP在体外可促进细胞增殖、迁移和侵袭，抑制细胞粘附和凋亡。实时荧光定量PCR结果显示：（1）细胞周期调控因子PCNA、cyclin D1和考克斯-2的mRNA表达水平在PNP处理的细胞中较对照组升高，而促凋亡基因Bax的mRNA表达水平降低;（2）EMT相关基因E-cadherin在PNP处理的细胞中表达水平降低，而N-cadherin、vimentin、snail和slug的mRNA表达水平升高;（3）促癌基因HIF-1、IL-1 β、VEGF α和K-Ras表达增强，抑癌基因p53、PTEN和BRCA表达降低。PNP暴露时间与促进效果之间存在正相关。最后，我们发现，在PNP处理的T24细胞中，PPAR γ（γ 1亚型）的表达水平增加。GW 9662是一种特异性的PPAR γ拮抗剂，可减弱PNP诱导的细胞迁移和侵袭。这些发现表明PNP暴露可能促进膀胱癌的生长和进展，涉及PPAR γ信号传导。PPAR-gamma是一个潜在的环境污染干预研究的新靶点。Environ.摩尔变异体61：316-328，2020. (c)2019 Wiley Periodicals，Inc.
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-1 beta, VEGF alpha 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 PPAR gamma (gamma 1 isoform) was increased in PNP-treated T24 cells. GW9662, a specific PPAR gamma antagonist, attenuated PNP-induced cell migration and invasion. These findings indicate that PNP exposure may promote bladder cancer growth and progression involving PPAR gamma signaling. PPAR gamma is a potential target for development of novel intervention study on environment pollution. Environ. Mol. Mutagen. 61:316-328, 2020. (c) 2019 Wiley Periodicals, Inc.