雌马酚对映异构体对大肠癌发生及大肠癌细胞增生、侵袭、和凋亡的影响及其作用机制研究

项目名称： 雌马酚对映异构体对大肠癌发生及大肠癌细胞增生、侵袭、和凋亡的影响及其作用机制研究

项目编号： No.81202193

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 马德福

作者单位： 北京大学

项目金额： 23万元

中文摘要： 近年发现大肠癌中雌激素受体ERα/β表达阳性后，有学者提出大肠癌是雌激素依赖性肿瘤。流行病学和实验研究均证实大豆异黄酮（SI）可通过雌激素活性抑制大肠癌发生。雌马酚(Eq)是SI及其代谢产物中雌激素活性最高的一种，有S、R两种异构体(代谢的天然产物均为S型，人工合成为二者消旋产物)，且两异构体与ERα/β结合力显著不同。我们以前的研究证实Eq对乳腺癌和前列腺癌发生有抑制作用，但Eq对大肠癌发生的影响及机制还不明确。因此本研究拟培养DLD1、HCT15、COLO205、LOVO、和SW480大肠癌细胞系，利用氧化偶氮甲烷诱导去势大鼠大肠癌，通过MTT等实验明确Eq对映异构体对大肠癌细胞增生、侵袭和凋亡的影响，并通过体内外研究探讨对雌激素受体通路，MAPK 和 PI3K信号传导通路等的影响；此外本研究还将采用特异性雌激素受体激动剂和抑制剂探讨雌激素受体ERα/β在大肠癌发生中的不同作用及机制。

中文关键词： 雌马酚；雌激素受体；雌激素样作用；大肠癌；金雀异黄素

英文摘要： Since the expression of ERα and ERβ was found in colon cancer tissues, some researchers proposed that the colon cancer may be an estrogen-dependant neoplasm. Epidemiological studies and experimental studies have proved that soy isoflavones can inhibit colon carcinogenesis through its estrogenic activity significantly. Equol is one of the materials with highest estrogenic activity among the isoflavones and its metabolites and has two enantiomers, R- and S- enantiomers (the nature metabolites are S-enantiomer, the artificial synthesis are racemic equol), which have significant different binding affinity with ERα and ERβ. Our previous studies have proved that equol can inhibit growth of breast and prostate cancer cells significantly. However, the effect and mechanisms of equol on the colon carcinogenesis are unclear. Therefore, we will culture DLD1, HCT15, COLO205, LOVO, and SW480 colon cancer cells, induce the colon cancer model by azoxymethane in ovariectominzed rats, determine the effect of the R- and S-enantiomers of equol on the proliferation, invasion, and apoptosis of colon cancer cells by MTT assay and so on, explore the underling mechanisms including the estrogen receptor pathway, MAPK signal pathway, and PI3K signal pathway etc., in vitro and in vivo in the present research. Morevoer, we will determine th

英文关键词： equol；estrogen receptor；estrogenic effect；colonic neoplasms；genistein