British Journal of Nutrition, 2013, 109(1):33-42.

Genistein, a soya isoflavone, prevents azoxymethane-induced up-regulation of WNT/b-catenin signalling and reduces colon pre-neoplasia in rats

Yukun Zhang, Qian Li, Dan Zhou, et al

Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 905 S. Goodwin Avenue, Bevier Hall Room 472, Urbana, IL 61801, USA

The present study aimed to explore the role(s) of the soya isoflavone genistein (GEN) in preventing the development of colon pre-neoplasia, using Wingless/int (WNT)/β-catenin as a molecular marker of colon abnormality. Specifically, the effects on the WNT/β-catenin signalling pathway from GEN were examined by using an azoxymethane (AOM)-induced rat colon cancer model. Male Sprague-Dawley rats were fed a control (CTL), a soya protein isolate (SPI) or a GEN diet from gestation to 13 weeks of age. The first sampling was conducted at 7 weeks of age for pre-AOM analysis. The remaining rats were injected with AOM at 7 weeks of age. The descending colon was collected 6 weeks later for the evaluation of aberrant crypt foci (ACF), gene expression and nuclear protein accumulation. AOM injection induced aberrant nuclear accumulation of β-catenin in the CTL group but not in the SPI or GEN group. Moreover, the WNT target genes Cyclin D1 and c-Myc were repressed by SPI and GEN. Meanwhile, SPI and GEN suppressed the expression of WNT signalling genes including Wnt5a, Sfrp1, Sfrp2 and Sfrp5 to the similar level to that of the pre-AOM period. Rats fed SPI and GEN had a decreased number of total aberrant crypts. GEN feeding also resulted in a reduced number of ACF with N = 3 per foci. The reduction of WNT/β-catenin signalling was correlated with the decrease in total aberrant crypts. By testing WNT/β-catenin signalling as a biomarker of colon carcinogenic potential, we showed the novel role of GEN as a suppressor of carcinogen-induced WNT/β-catenin signalling in preventing the development of early colon neoplasia.

英国《英国营养学杂志》，2013年1月

金雀异黄素，一种大豆异黄酮，可以阻止氧化偶氮甲烷诱导的WNT/b-连环蛋白信号的上调并降低大鼠的结肠癌病变

张玉坤， 李倩，周丹，等

美国伊利诺伊大学厄巴纳-尚佩恩分校食品科学和人类营养学院

本研究旨在探讨大豆异黄酮金雀异黄素 (GEN)在预防结肠癌病变方面的作用，使用无翅基因/int (WNT) / β-蛋白作为结肠异常的分子标记。具体来说，使用氧化偶氮甲烷 (AOM) 诱导的大鼠结肠肿瘤模型考察了GEN对WNT/β-catenin 信号通路的影响。从妊娠到 13 周分别喂食雄性大鼠对照 (CTL)、 大豆分离蛋白 (SPI) 或GEN饮食。在 7 周龄前 为了AOM预 分析进行了第一次采样。剩下的大鼠在 7 周龄时注射AOM。6 周以后收集下行的结肠来评价异常的隐窝病灶 (ACF)、 基因表达和核蛋白质的积累。AOM 注射诱导了β-catenin在CTL 组而不是在 SPI 或GEN组中异常的核积累。此外，WNT 靶基因细胞周期蛋白 D1 和 c-Myc 被 SPI 和GEN 抑制。同时，SPI 和GEN抑制了WNT 信号基因包括 Wnt5a、 Sfrp1、 Sfrp2 和 Sfrp5的表达到与 AOM之前类似的水平。喂养SPI 和GEN的大鼠的异常隐窝总数减少。GEN 喂养也导致ACF的数量减少。WNT/β-catenin 信号减少与异常隐窝综述减少相关。通过测试结肠癌变潜力的生物标志物WNT/β-catenin的 信号，我们认为GEN可以抑制致癌物诱导的 WNT/β-catenin 信号从而阻止早期结肠肿瘤的发展。