P556 Endogenous conversion of ω-6 to ω-3 polyunsaturated fatty acids in fat-1 mice attenuated intestinal polyposis by either inhibiting COX-2/β-catenin signalling or activating IL-18
K. B. Hahm*1, Y. J. Kim2, J.M. Park1
1CHA University, Gastroenterology, Seongnam, South Korea, 2Gachon University, Gastroenterology, Incheon, South Korea
The omega-3 polyunsaturated fatty acids (ω-3PUFAs) have been known to have inhibitory actions against various preclinical cancer models, but their effects on intestinal polyposis are unknown. Because the nutritional intervention has been tried to counteract colon cancer development, in this study, we evaluated the effects of ω-3PUFAs on intestinal polyposis of an APC/Min+ mice model, using experimental groups including wild-type C56BL/6 mice, APC/Min+ mice, fat-1 transgenic mice overexpressedn-3 desaturase enable to synthesise ω-3 PUFAs, and APC/Min+ x fat-1 double-TG mice at 20 weeks of age.
Small intestines were collected for gross and pathologic evaluation, including polyp number and size, followed with immunohistochemical staining and Western blot for COX-2, 15-PGDH, IL-1β, IL-18, β-catenin/GSK3β, Tcf-4, and Lef-1 expressions. Measuring PUFAs with exogenous administration of various concentrations of ω-3 PUFAs was done to compare PUFA concentrations synthesised in the small intestine of fat-1 mice.
ω-3 PUFAs significantly attenuated Apc mutation-induced intestinal polyposis (p < 0.005), in which significant inhibition of Wnt/beta-catenin signalling was noted, accompanied with significant inhibition of COX-2 and PGE2, and significant induction of 15-PGDH (p < 0.01). In addition, significant apoptosis consequent to significant induction of inflammasome, including IL-1β, caspase-3, and IL-18, was observed in APC/Min+ x fat-1 double-transgenic mice. The exogenous administration more than 3 g/60 kg ω-3 PUFAs was equivalent to those produced in fat-1 transgenic mice and showed significant expressions of IL-1β, capspase-3, and IL-18, as seen in APC/Min+ x fat-1 double-TG mice.
ω-3 PUFAs, authentic synthesis, or intake of more than 3 g/60 kg body weight effectively attenuated intestinal polyposis in APC/Min+ supports omega-3 PUFAs, and intake can be a faithful clinical surveillance strategy in patients with polypectomy because of intestinal polyp.