The proceedings of the International Symposium on Metropolis :. National Institute for Research Advancement, 1984:3815-3826.

Genistein suppressed epithelial–mesenchymal transition and migration efficacies of BG-1 ovarian cancer cells activated by estrogenic chemicals via estrogen receptor pathway and downregulation of TGF-β signaling pathway

Ye-Seul Kim, Kyung-Chul Choi, et al

Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea

BACKGROUND:

Epithelial-mesenchymal transition (EMT), which is activated by 17β-estradiol (E2) in estrogen-responsive cancers, is an important process in tumor migration or progression. As typical endocrine disrupting chemicals (EDCs), bisphenol A (BPA) and nonylphenol (NP) have a potential to promote EMT and migration of estrogen-responsive cancers. On the contrary, genistein (GEN) as a phytoestrogen is known to have chemopreventive effects in diverse cancers.

METHODS:

In the present study, the effects of BPA and GEN on EMT and the migration of BG-1 ovarian cancer cells and the underlying mechanism were investigated. ICI 182,780, an estrogen receptor (ER) antagonist, was co-treated with E2 or BPA or NP to BG-1 cells to identify the relevance of ER signaling in EMT and migration.

RESULTS:

As results, E2 and BPA upregulated the protein expression of vimentin, cathepsin D, and MMP-2, but downregulated the protein expression of E-cadherin via ER signaling pathway, suggesting that E2 and BPA promote EMT and cell migration related gene expressions. However, the increased protein expressions of vimentin, cathepsin D, and MMP-2 by E2, BPA, or NP were reduced by the co-treatment of GEN. In a scratch assay, the migration capability of BG-1 cells was enhanced by E2, BPA, and NP via ER signaling but reversed by the co-treatment of GEN. In the protein expression of SnoN and Smad3, E2, BPA, and NP upregulated SnoN, a negative regulator of TGF-β signaling, and downregulated pSmad3, a transcription factor in the downstream pathway of TGF-β signaling pathway, suggesting that E2, BPA, and NP simultaneously lead to the downregualtion of TGF-β signaling in the process of induction of EMT and migration of BG-1 cells via ER signaling. On the other hand, the co-treatment of GEN reversed the downregulation of TGF-β signaling by estrogenic chemicals.

CONCLUSION:

Taken together, GEN suppressed EMT and migration capacities of BG-1 ovarian cancer cells enhanced by E2, BPA, and NP via ER signaling and the downregulation of TGF-β signal.

《大都会国际研讨会会议记录》，2015年10月

金雀异黄素抑制了由雌激素化学物质通过雌激素受体途径和下调 TGF-β 的信号转导通路激活的BG-1卵巢癌细胞上皮-间充质的转换和迁移功效

金秀玲，崔京珠，等

韩国中央大学兽医学院生物化学与免疫学实验室

背景：

在雌激素反应性癌症中由17β-雌二醇（E2）激活的上皮间质转化（EMT）是肿瘤迁移或进展的重要过程。 作为典型的内分泌干扰物质（EDCs），双酚A（BPA）和壬基酚（NP）具有促进雌激素反应性癌症EMT和迁移的潜力。 相反，已知金雀异黄素（GEN）作为植物雌激素在多种癌症中具有化学预防作用。

方法：

在本研究中，研究了BPA和GEN对EMT和BG-1卵巢癌细胞迁移的影响及其机制。 用E2或BPA或NP与BG-1细胞共同处理雌激素受体（ER）拮抗剂ICI 182,780，以确定ER信号在EMT和迁移中的相关性。

结果：

结果表明，E2和BPA上调波形蛋白，组织蛋白酶D和MMP-2的蛋白表达，但通过ER信号通路下调E-钙粘蛋白的蛋白表达，表明E2和BPA促进EMT和细胞迁移相关基因表达。然而，通过与GEN共同处理，减少了由E2，BPA或NP增加的波形蛋白，组织蛋白酶D和MMP-2的蛋白质表达。在划痕试验中，ER信号通过E2，BPA和NP增强BG-1细胞的迁移能力，但是通过GEN的共同治疗反转。在SnoN和Smad3，E2，BPA和NP的蛋白表达中，上调TGF-β信号传导的负调节物SnoN，并下调pSmad3，TGF-β信号通路下游途径转录因子，表明E2，BPA ，NP同时导致TGF-β信号转导通过ER信号诱导EMT和BG-1细胞迁移过程。另一方面，GEN的共同治疗反转了雌激素化学物质对TGF-β信号传导的下调。

结论：

总之，GEN抑制由E2，BPA和NP通过ER信号增强的BG-1卵巢癌细胞的EMT和迁移能力以及TGF-β信号的下调。