Objectives.双酚A(BPA)是一种不可缺少的工业化学品。然而,作为一种公认的内分泌干扰物,它可能与一些健康问题有关,包括生殖功能受损和癌症。由于BPA使用的限制,许多双酚衍生物逐渐取代BPA。然而,研究报告了BPA类似物的不良生物学效应,但是他们行动的具体地点仍然未知。核受体(NRs)似乎在各种类型的癌症中起重要作用。此外,它们被认为是双酚的相关目标。在本研究中,我们研究了BPA及其类似物双酚S(BPS)的作用,双酚F(BPF),双酚AF(BPAF)对人卵巢上皮细胞系Caov3中NRsmRNA表达的影响。检查的NRs包括视黄酸受体α(RARA),类视黄醇X受体α(RXRA),过氧化物酶体增殖物激活受体β/δ(PPARD),鸡卵清蛋白上游启动子转录因子2(COUPTFII),和核受体相关蛋白1(NURR1)。方法。Caov3细胞用浓度为1nM的双酚处理,100nM,10µM和100µM。孵育24小时和72小时后,通过MTS测定确定细胞活力,并且使用RT-qPCR分析所选择的基因表达。结果。双酚处理不影响Caov3细胞活力,除了暴露于最高BPAF剂量(100µM)后的显着损害。在较低的剂量下,两种双酚类似物均未改变NRs的表达。然而,在最高浓度(100µM),BPAF和BPA改变了PPARD的mRNA水平,COUPTFII,和NURR1以时间和受体特异性方式。Conclusions.本研究首次讨论了双酚对上皮性卵巢癌细胞中特定NRs的影响。虽然通常我们没有发现双酚可能引起Caov3细胞中所选NRs表达的显著改变,它们可能会改变高浓度下某些NRs的mRNA表达。
Objectives. Bisphenol A (BPA) is an indispensable industrial chemical. However, as a proven endocrine disruptor, it may be associated with several health disturbances, including the reproductive functions impairment and cancer. Due to the restriction of BPA usage, many bisphenol derivatives gradually substitute BPA. However, studies have reported adverse biological effects of BPA analogs, but the specific sites of their action remain largely unknown. Nuclear receptors (NRs) appear to play significant roles in various types of cancer. In addition, they are considered relevant targets of bisphenols. In the present study, we investigated the effects of BPA and its analogs bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) on mRNA expression of selected NRs in the human ovarian epithelial cell line Caov3. The NRs examined included retinoic acid receptor α (RARA), retinoid X receptor α (RXRA), peroxisome proliferator activating receptor β/δ (PPARD), chicken ovalbumin upstream promoter-transcription factor 2 (COUPTFII), and nuclear receptor-related protein 1 (NURR1). Methods. Caov3 cells were treated with the bisphenols at the concentrations of 1 nM, 100 nM, 10 µM and 100 µM. After 24 h and 72 h of incubation, cell viability was determined by the MTS assay, and the selected genes expression was analyzed using RT-qPCR. Results. Bisphenol treatment did not affect Caov3 cell viability, except the significant impairment after exposure to the highest BPAF dose (100 µM). At lower doses, neither bisphenol analog altered the expression of the NRs. However, at the highest concentration (100 µM), BPAF and BPA altered the mRNA levels of PPARD, COUPTFII, and NURR1 in a time- and receptor-specific manner. Conclusions. The effects of bisphenols on the specific NRs in the epithelial ovarian cancer cells were addressed for the first time by the present study. Although generally we did not find that bisphenols may provoke significant alterations in the expression of the selected NRs in Caov3 cells, they may alter mRNA expression of certain NRs at high concentrations.