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

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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.