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氟维司群与低剂量 BPA 的联合作用:对 HepG2 细胞 EMT、细胞凋亡和 TGF-β1 信号转导的比较影响。

Combined effect of fulvestrant and low dose BPA: comparative implications on EMT, apoptosis, and TGF-β1 signaling in HepG2 cells.

机构信息

Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.

出版信息

Drug Chem Toxicol. 2022 Sep;45(5):2285-2291. doi: 10.1080/01480545.2021.1935368. Epub 2021 Jun 8.

DOI:10.1080/01480545.2021.1935368
PMID:34100320
Abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical utilized in the manufacture of food packaging, dental materials, medical devices, children's toys, and baby products. Numerous studies have indicated the role of BPA in the etiology of many diseases such as diabetes, cardiovascular diseases, obesity, cancer, and chemotherapeutic resistance. However, the effects of BPA- chemotherapeutic combination remain to be investigated in different cell lines. Here, we demonstrate that low dose BPA and fulvestrant (estrogen receptor antagonist) combination synergistically decrease proliferation, promote cell migration and mesenchymal transition, switching from E-cadherin to N-cadherin expression Hepg2 cells. Moreover, we determined that low dose BPA may evoke susceptibility to apoptosis in HepG2 cells. The mechanism underlying these effects has been identified as increased TGF-β1 signaling. Our results provide an experimental basis for evaluating the potential health risks of low-dose BPA for fulvestrant therapy in hepatocytes.

摘要

双酚 A (BPA) 是一种内分泌干扰化学物质,用于制造食品包装、牙科材料、医疗器械、儿童玩具和婴儿产品。许多研究表明 BPA 在许多疾病的病因学中起作用,如糖尿病、心血管疾病、肥胖症、癌症和化疗耐药性。然而,BPA-化疗联合治疗的效果在不同的细胞系中仍有待研究。在这里,我们证明低剂量 BPA 和氟维司群(雌激素受体拮抗剂)联合协同降低增殖,促进细胞迁移和间充质转化,从 E-钙粘蛋白切换到 N-钙粘蛋白表达 Hepg2 细胞。此外,我们确定低剂量 BPA 可能使 HepG2 细胞易发生细胞凋亡。这些作用的机制已被确定为 TGF-β1 信号的增加。我们的结果为评估低剂量 BPA 对肝细胞中氟维司群治疗的潜在健康风险提供了实验依据。

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