The effect of generational feeding of soy and genistein-supplemented diets on progression of precancerous lesions in colon of second generation male rats

Genistein;colon cancer;generational animal model;nutrient-gene interaction;aberrant crypt foci;soy protein isolate;Wnt signaling pathway

Jorud, Ingrid ; Chen ; Hong

关键词: Genistein;    colon cancer;    generational animal model;    nutrient-gene interaction;    aberrant crypt foci;    soy protein isolate;    Wnt signaling pathway;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/30913/Jorud_Ingrid.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Colon cancer is the third leading cause of cancer related death in the United States. Epidemiological evidence has shown that populations who consume a traditional East Asian diet high in soy isoflavones have a reduced incidence of developing colon cancer. In previous studies, soy and isoflavones have also been shown to have an effect on reducing colon cancer growth and progression in vitro and in vivo.This study used Sprague Dawley male rats from the second generation of a multiple generation model, which were fed a control, soy, or genistein-supplemented diet.Soy and genistein fed rats had dietary exposure from two previous generations, consumed the same diet and therefore were exposed through gestation, lactation, and post-weaning.Control group rats were obtained at six weeks of age.At ten weeks of age, the rats were injected with azoxymethane (AOM) and were sacrificed at fifteen weeks.Descending colon tissue was collected for physiological, protein, and genetic analysis.Identification of aberrant crypt foci (ACF) was used to determine physiological effect and stage of precancerous progression.Rats fed soy or genistein diets showed significant decrease of total numbers of ACF and reduced multiplicity.Established members of the Wnt signaling pathway, including inhibitors and targets, were analyzed using mRNA expression.Wnt16, Wnt8b, Wnt1, sFRP5, and Dkk1 were significantly increased in the genistein group compared to control and Cyclin D1 was significantly decreased in soy and genistein groups compared to control.β-catenin was used as the protein indicator of Wnt pathway activation.Rats fed a soy or genistein diet showed a significant reduction of nuclear β-catenin.In rats fed soy and genistein diets, advanced stages of ACF decreased, as well as Cyclin D1 expression and nuclear β-catenin also decreased – indicating a reduction in precancerous progression.