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

背景和目的：流行病学数据和实验研究表明，脂肪摄入量和摄入的膳食脂肪酸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氧化偶氮甲烷（AOM）诱发大鼠结肠癌的影响。材料与方法：雄性SD大鼠腹腔注射AOM 15 mg/kg体重，每周1次，共2次。用标准普通饲料基础饲料或添加10%玉米油、10%橄榄油、10%牛肉油或10%鱼油的普通饲料喂养大鼠44周。12周时检查结肠异常隐窝病灶（ACF），44周时检查致癌性。结果如下：在AOM治疗的大鼠中，膳食玉米油和牛肉油在12周时增加了ACF的形成，并且在44周时结肠癌的数量显着增加。相比之下，饮食橄榄油和鱼油在12周时降低了ACF形成，并且AOM治疗的大鼠在44周时结肠癌发病率和多样性均降低。在44周时，细胞周期蛋白D1和胞浆β-连环蛋白的表达显着增加，大鼠喂养的饮食玉米和牛肉油。饮食牛肉油增加粘膜Wnt 2，3和玉米油增加粘膜Wnt 5a。结论：在AOM处理的大鼠中，长期饮食饱和脂肪酸n-6多不饱和脂肪酸通过上调Wnt/β-连环蛋白信号传导增加细胞增殖而加速氧化偶氮甲烷诱导的结肠癌发生。相反，n-9 MUFA和n-3 PUFA对结肠癌的发生具有抑制作用。

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.