Individual and Combined Effect of Bisphenol A and Bisphenol AF on Prostate Cell Proliferation through NF-κB Signaling Pathway
International Journal of Molecular Sciences(2022)
摘要
The ubiquitous environmental endocrine disruptor bisphenol A (BPA) can induce prostatic dysfunction. However, to date, studies have focused little on the perturbations of prostate health initiated by the BPA derivative bisphenol AF (BPAF) and co-exposure to bisphenol compounds. An in vivo study orally administrated male rats with BPA (10, 90 μg/kg), BPAF (10, 90 μg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg). Based on the anatomical analysis, pathological observations and PCNA over-expression, we considered that low-dose BPA and BPAF facilitated ventral prostatic hyperplasia in rats. The results of IHC and ELISA mirrored the regulation of NF-κB p65, COX-2, TNF-α and EGFR in BPA- and BPAF-induced prostatic toxicity. An in vitro study found that the additive effect of combined exposure to BPA (10 nM) and BPAF (10 nM) could cause an elevation in the proliferation of and a reduction in the apoptosis level of human prostate stromal cells (WPMY−1) and fibroblasts (HPrF). Meanwhile, the underlying biomarkers of the NF-κB signaling pathway also involved the abnormal proliferative progression of prostate cells. The findings recapitulated the induction of BPAF exposure and co-treatment with BPA and BPAF on prostatic hyperplasia and emphasized the modulation of the NF-κB signaling pathway.
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关键词
bisphenols,prostatic hyperplasia,co-exposure,nuclear transcription factor-κB,cyclooxygenase-2
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