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.
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.
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.
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.
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.
Kim YS
，Choi KC
，Hwang KA
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An evidence in vitro for the influence of bisphenol A on uterine leiomyoma.
To study the effect and mechanism of environmental estrogens bisphenol A (BPA) on uterine leiomyoma (UL) cells.
Primary cultures and subcultures of human UL cells, which were identified by immunocytochemical staining with a monoclonal anti-α-smooth muscle actin antibody, were performed. The viability of cells in different concentration of bisphenol A of 24h, 48h and 72h were analyzed by CCK-8. The expressions of mRNA of ERα, IGF-1 and VEGF in all groups were detected by real-time quantitative PCR assay, and then the expressions of proteins detected by Western blot assay.
BPA promoted the growth of UL cells and the expressions of ERα, IGF-1 and VEGF, which had positive correlation with the concentration and action time of BPA treatment.
BPA promotes the growth of leiomyoma cells. The expressions of IGF-1, VEGF can be up-regulated by ERα, which may be possible mechanism of BPA promote the growth of leiomyoma cells.
Shen Y
，Ren ML
，Feng X
，Cai YL
，Gao YX
，Xu Q
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