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

流行病学研究表明，高膳食脂肪摄入促进结肠癌。最近的证据支持这样的理论，即肿瘤在体内的生长依赖于逃避正常的稳态控制机制，该机制通过细胞凋亡诱导细胞死亡而起作用。本研究的目的是调查长期食用油对结肠癌发生和癌症发展的影响。雄性Sprague-Dawley大鼠注射结肠致癌物氧化偶氮甲烷（AOM），并喂食10%的油48周。对结肠异常隐窝病灶和肿瘤进行组织病理学检查，并对细胞凋亡和增殖进行评价。采用RT-PCR、免疫沉淀和Western blotting等方法研究野生型p53基因的作用。长期食用玉米油和牛肉油通过腺瘤-癌序列促进结肠癌发生。大鼠结肠表现为分化良好的腺癌，并伴有粘膜下浸润。玉米和牛肉油可促进AOM处理大鼠结肠粘膜增殖，抑制结肠粘膜凋亡。AOM可增加结肠MDM 2的表达，MDM 2可促进p53降解，或与胞浆中的p53结合并使其失活。结果表明，长期饮食玉米油和牛肉油促进结肠癌的发生和癌症的发展，部分通过抑制细胞凋亡。

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.