Long-term oil ingestion promotes invasive colon cancer by inhibiting in azoxymethane-treated rats

流行病学研究表明，饮食中摄入大量脂肪会导致结肠癌。最近的证据支持这一理论，即肿瘤在体内的生长依赖于通过细胞凋亡诱导细胞死亡来逃避正常的稳态控制机制。本研究旨在探讨长期食用油脂对结肠癌发生和癌症发展的影响。雄性Sprague-Dawley大鼠注射结肠癌致癌物偶氮氧甲烷（azoxymethane， AOM），饲喂10%油48周。对结肠异常隐窝灶和肿瘤进行组织病理学检查，并观察细胞凋亡和增殖情况。采用RT-PCR、免疫检测和Western blotting等方法研究野生型p53的作用。长期食用玉米油和牛油通过腺瘤-癌序列促进结肠癌的发生。大鼠结肠表现为粘膜下浸润的高分化腺癌。玉米油和牛油可促进aom处理大鼠结肠黏膜增殖，抑制结肠黏膜凋亡。AOM增加结肠多重双分钟-2(MDM2)， MDM2促进p53降解，或在细胞质中结合和灭活p53。结果提示，长期饲粮玉米油和牛油促进结肠癌的发生和发展，部分原因是抑制细胞凋亡。

Epidemiological studies have suggested that a high dietary fat intake promotes colon cancer. Recent evidence supports the theory that tumor growth in vivo depends on evading the normal homeostatic control mechanisms operating through induction of cell death by apoptosis. The aim of this study was to investigate the effect of long-term dietary oil on colonic carcinogenesis and cancer development. Male Sprague-Dawley rats were injected with the colon carcinogen azoxymethane(AOM), and fed 10% oil for 48 weeks. Colonic aberrant crypt foci and tumors were examined histopathologically, and cellular apoptosis and proliferation were evaluated. The role of wild type p53 was studied using RT-PCR, immunopercipition and Western blotting. Long-term dietary corn oil and beef oil promoted colonic carcinogenesis via an adenoma-carcinoma sequence. The rat colons showed well-differentiated adenocarcinoma with submucosal invasion. The dietary corn and beef oil enhanced colonic mucosal proliferation, and inhibited colonic mucosal apoptosis in AOM-treated rats. AOM increased colonic multiple double minute-2(MDM2), and the MDM2 promoted p53 degradation, or bound and inactivated p53 in the cytosol. The results suggest that long-term dietary corn oil and beef oil promotes colonic carcinogenesis and cancer development partly by inhibiting apoptosis.