植物雌激素在雌性生殖系统中的抗氧化作用  

Induction of antioxidant activity by phytoestrogens in female reproductive system

作　　者：余波澜[1] 郑婷[1] 蒋露[1] 

机构地区：[1]广州医科大学附属第三医院产科,广东省产科重大疾病重点实验室,广东省普通高校生殖与遗传重点实验室,广州510150

出　　处：《广东医学》2014年第21期3289-3293,共5页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81102474)

摘　　要：目的探讨植物雌激素白藜芦醇、染料木黄酮和大豆黄酮在人类宫颈癌细胞He La、乳腺癌细胞MCF7和卵巢癌细胞SK-OV-3中对抗氧化信号通路的影响。方法将抗氧化响应元件ARE报告基因转染入He La、MCF7和SK-OV-3细胞。稳定表达ARE荧光报告基因后,细胞培养基中分别加入50、25、12.5、6.25、3.125、1.56和0μmol/L的3种植物雌激素,检测ARE诱导倍数的变化。分别检测3种植物雌激素24 h处理后诱导细胞中抗氧化基因Nrf2、SOD1、SOD2、SOD3、HO-1、GSTm、GSTp、NQO1、CAT和CLGC等的mRNA表达水平。在MCF7细胞中,检测25μmol/L的白藜芦醇和大豆黄酮对野生型Keap1蛋白抑制Nrf2-ARE表达的影响。结果在MCF7、He La和SK-OV-3细胞中,3种植物雌激素均能诱导ARE报告基因的高表达,并促进Nrf2、SOD3、GSTp、CAT和CLGC等抗氧化基因的高表达。同时,25μmol/L的白藜芦醇和大豆黄酮在MCF7细胞中能够有效淬灭Keap1蛋白对ARE表达的抑制作用。结论植物雌激素白藜芦醇、染料木黄酮和大豆黄酮能够在人类宫颈癌细胞He La、乳腺癌细胞MCF7和卵巢癌细胞SK-OV-3中诱导抗氧化信号通路。诱导效应具有剂量依赖性和组织特异性。转录调控蛋白Keap1可能参与了诱导反应机制。Objective To investigate the effects of phytoestrogens, including resveratrol, genistein, and daid- zein, on the antioxidant signaling pathways in human ovary, uterus, and breast cancer cells. Methods HeLa, MCF7 and SK - OV - 3 cells transduced with antioxidant response element （ARE） reporter were treated with phytoestrogens by 50, 25, 12.5, 6.25, 3. 125, 1.56 and 0 μmol/L. The ARE was examined, and the mRNA expression levels of Nrf2, SOD1, SOD2, SOD3, HO - 1, GSTm, CSTp, NQO1, CAT and CLCC were analyzed. In MCF7 cells, the quenching effects of resveratrol and daidzein on the inhibitive effects of Keapl on Nrt2 - ARE were observed. Results Phytoestro- gens could induce ARE activity and mRNA expression of Nef2, SOD3, GSTp, CAT and CLGC in MCF7, HeLa, and SK - OV - 3 cells. In addition, resveratrol and daidzein at 25 μmol/L could quench the inhibitive effects of Keapl on ARE expression. Conclusion Phytoestrogen genistein, daidzein and resveratrol could activate antioxidant - signaling pathway in HeLa, MCF7, and SK- OV -3 cells in dose and tissue -specific dependent manners. Regulatory protein Keapl may be involved in their antioxidant mechanisms.

关 键 词：植物雌激素 抗氧化 KEAP1 

分 类 号：R285.5[医药卫生—中药学]