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Dietary saturated fatty acid n-6 poly-unsaturated fatty acid accelerate azoxymethane induced colon carcinogenesis through up-regulation of Wnt/beta-catenin signaling

膳食饱和脂肪酸 n-6 多不饱和脂肪酸通过上调 Wnt/β-catenin 信号传导加速氧化偶氮甲烷诱导的结肠癌发生

基本信息

批准号：
16590605
负责人：
IWAKIRI Ryuichi
金额：
$ 1.92万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Background and Aim : Epidemiological data and experimental studies have shown that both the amount of fat intake and the composition of ingested dietary fatty acids are crucial to colon carcinogenesis. The aim of this study is to investigate the effect of various dietary fats on colon carcinogenesis in azoxymethane (AOM) treated rat. Materials and Methods : Fifteen mg/kg body wt of AOM was intraperitoneally injected to male SD rats once a week for 2 times. Rats were fed with standard chow basal diet or chaw supplemented with 10% of corn oil, 10% of olive, 10% of beef oil or 10% of fish oil for 44 weeks. Colonic aberrant crypt foci (ACF) were examined at 12 weeks and carcinogenecity was examined at 44 weeks. Results : Dietary corn oil and beef oil increased ACF formation in AOM-treated rats at 12 weeks and numbers of colon cancers are significantly increased at 44 weeks. In contrast, both dietary olive oil and fish oil decreased ACF formation at 12 weeks and both colon cancer incidence and multiplicity were decreased in AOM treated rats at 44 weeks. At 44 weeks, cyclin D1 and cytosolic beta-catenin protein expression were significantly increased in rats fed with dietary corn and beef oil. Dietary beef oil increased mucosal Wnts 2, 3 and corn oil increased mucosal Wnt5a. Conclusion : Long term dietary saturated fatty acid n-6 poly-unsaturated fatty acid accelerate azoxymethane induced colon carcinogenesis by increasing cell proliferation through up-regulating Wnt/beta-catenin signaling in AOM treated rats. In contrast, n-9 MUFA and n-3 PUFA had suppressive effects for colon carcinogenesis.

背景与目的：流行病学资料和实验研究表明，脂肪摄入量和膳食脂肪酸的组成对结肠癌的发生至关重要。本研究旨在探讨不同膳食脂肪对偶氮氧甲烷（AOM）处理大鼠结肠癌发生的影响。材料与方法：雄性SD大鼠腹腔注射AOM 15 mg/kg体wt，每周1次，共2次。大鼠分别饲喂标准基础日粮或添加10%玉米油、10%橄榄油、10%牛油或10%鱼油的日粮44周。12周时检查结肠异常隐窝灶（ACF）， 44周时检查致癌性。结果：玉米油和牛油增加了aom处理大鼠在12周时ACF的形成，在44周时结肠癌的数量显著增加。相比之下，饮食中橄榄油和鱼油在12周时都减少了ACF的形成，在44周时，AOM治疗大鼠的结肠癌发病率和多样性都降低了。44周时，玉米和牛油组大鼠细胞周期蛋白D1和细胞质β -连环蛋白表达显著升高。饲粮中牛肉油增加了粘膜wnt2、3，玉米油增加了粘膜Wnt5a。结论：长期食用饱和脂肪酸n-6多不饱和脂肪酸通过上调Wnt/ β -catenin信号通路，促进偶氮氧甲烷诱导的大肠癌的发生。相反，n-9 MUFA和n-3 PUFA对结肠癌的发生有抑制作用。