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Combined effect of fulvestrant and low dose BPA: comparative implications on EMT, apoptosis, and TGF-β1 signaling in HepG2 cells
Drug and Chemical Toxicology ( IF 2.1 ) Pub Date : 2021-06-08 , DOI: 10.1080/01480545.2021.1935368
Esin Öz 1 , Tuba Tüylü Küçükkılınç 2
Affiliation  

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.



中文翻译:

氟维司群和低剂量 BPA 的联合作用:对 HepG2 细胞中 EMT、细胞凋亡和 TGF-β1 信号传导的比较意义

摘要

双酚 A (BPA) 是一种内分泌干扰化学品,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。大量研究表明 BPA 在许多疾病的病因学中发挥作用,例如糖尿病、心血管疾病、肥胖症、癌症和化疗耐药性。然而,BPA-化疗组合的效果仍有待在不同细胞系中进行研究。在这里,我们证明低剂量 BPA 和氟维司群(雌激素受体拮抗剂)组合可协同降低增殖,促进细胞迁移和间充质转化,从 E-cadherin 转换为 N-cadherin 表达 Hepg2 细胞。此外,我们确定低剂量 BPA 可能会引起 HepG2 细胞凋亡的易感性。这些作用背后的机制已被确定为增加的 TGF-β1 信号传导。我们的结果为评估低剂量 BPA 用于肝细胞中氟维司群治疗的潜在健康风险提供了实验基础。

更新日期:2021-06-08
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