金雀异黄素通过抑制雌激素受体 α 和胰岛素样生长因子-1 受体信号转导通路之间的串扰对17 β-雌二醇或双酚 A诱导的BG-1 卵巢癌生长发挥抗癌作用_黄京亚

针对病种：卵巢癌

发表时间：2013年11月

发表国家：美国

登载刊物：毒理学与应用药理学

研究单位：韩国忠北国立大学兽医学院兽医生化和免疫学实验室

研究人员：黄京亚，朴敏之、康南熙，等

主要结论：在本研究中，根据这种串扰的影响，我们评估了双酚 A (BPA)的雌激素效应的和金雀异黄素（GEN）的抗增殖活性。总之，这些结果表明，GEN通过抑制由BPA 或 E2 上调的ERα 和IGF-1R 的串扰信号转导通路，有效地逆转了 BG-1 卵巢癌增强的增殖.

Toxicology & Applied Pharmacology, 2013, 272(3):637-46.

Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 β-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor alpha and insulin-like growth factor-1 receptor signaling pathways

Kyung A Hwang, Min Ah Park, Nam Hee Kang, et al

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

The interaction between estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathway plays an important role in proliferation of and resistance to endocrine therapy to estrogen dependent cancers. Estrogen (E2) upregulates the expression of components of IGF-1 system and induces the downstream of mitogenic signaling cascades via phosphorylation of insulin receptor substrate-1 (IRS-1). In the present study, we evaluated the xenoestrogenic effect of bisphenol A (BPA) and antiproliferative activity of genistein (GEN) in accordance with the influence on this crosstalk. BPA was determined to affect this crosstalk by upregulating mRNA expressions of ERα and IGF-1R and inducing phosphorylation of IRS-1 and Akt in protein level in BG-1 ovarian cancer cells as E2 did. In the mouse model xenografted with BG-1 cells, BPA significantly increased a tumor burden of mice and expressions of ERα, pIRS-1, and cyclin D1 in tumor mass compared to vehicle, indicating that BPA induces ovarian cancer growth by promoting the crosstalk between ER and IGF-1R signals. On the other hand, GEN effectively reversed estrogenicity of BPA by reversing mRNA and protein expressions of ERα, IGF-1R, pIRS-1, and pAkt induced by BPA in cellular model and also significantly decreased tumor growth and in vivo expressions of ERα, pIRS-1, and pAkt in xenografted mouse model. Also, GEN was confirmed to have an antiproliferative effect by inducing apoptotic signaling cascades. Taken together, these results suggest that GEN effectively reversed the increased proliferation of BG-1 ovarian cancer by suppressing the crosstalk between ERα and IGF-1R signaling pathways upregulated by BPA or E2.

美国《毒理学与应用药理学》，2013年11月

金雀异黄素通过抑制雌激素受体 α 和胰岛素样生长因子-1 受体信号转导通路之间的串扰对17 β-雌二醇或双酚 A诱导的BG-1 卵巢癌生长发挥抗癌作用

黄京亚，朴敏之、康南熙，等

韩国忠北国立大学兽医学院兽医生化和免疫学实验室

雌激素受体 (ER) 和胰岛素样生长因子-1 受体 (IGF-1R) 信号转导通路的相互作用在增殖和抗内分泌治疗雌激素依赖性癌症方面发挥重要作用。通过胰岛素受体底物-1 (IRS-1)的磷酸化，雌激素 (E2) 上调了IGF-1 体系组分的表达并诱导有丝分裂下游的信号级联。在本研究中，根据这种串扰的影响，我们评估了双酚 A (BPA)的雌激素效应的和金雀异黄素（GEN）的抗增殖活性。确定BPA通过上调ERα和IGF-1的mRNA表达和BG-1 卵巢癌细胞中E2导致的IBS-1 和Akt 的磷酸化影响这种串扰。在 BG-1 细胞移植小鼠模型中，与空白样相比，BPA 显著增加了小鼠肿瘤的重量以及ERα，pIRS-1，和细胞周期蛋白 D1 在肿瘤体积上的表达，表明BPA 通过促进 ER 和IGE-1 受体的信号之间的交联诱导卵巢癌细胞生长。另一方面，GEN通过扭转 mRNA 和蛋白表达ERα，IGE-1R，pIRS-1，和 pAkt的表达有效地扭转了BPA的雌激素样作用，并明显降低了肿瘤的生长和体内ERα，IGE-1R，pIRS-1，和 pAkt在裸鼠移植小鼠模型中的表达。此外，通过诱导凋亡信号级联GEN已被证实具有抗增殖作用。总之，这些结果表明，GEN通过抑制由BPA 或 E2 上调的ERα 和IGF-1R 的串扰信号转导通路，有效地逆转了 BG-1 卵巢癌增强的增殖。