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

流行病学研究表明，饮食中脂肪的高摄入量会促进结肠癌。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体内平衡控制机制，这些机制是通过诱导细胞凋亡来实现的。本研究的目的是探讨长期食用食用油对结肠癌发生和发展的影响。雄性SD大鼠注射致癌物质偶氮甲烷(AOM)，饲喂10%油，连续48周。对结肠异常隐窝病灶和肿瘤进行组织病理学检查，并检测细胞凋亡和增殖情况。采用RT-PCR、免疫组化和Western blotting等方法研究野生型P53的作用。长期饮食玉米油和牛肉油通过腺瘤-癌序列促进结肠癌的发生。大鼠结肠呈高分化腺癌，并伴有黏膜下侵犯。饲料中添加玉米油和牛肉油可促进AOM处理大鼠结肠粘膜的增殖，抑制结肠粘膜的凋亡。AOM使结肠多重双分钟-2(MDM2)增加，MDM2促进P53的降解或胞浆中P53的结合和失活。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，部分是通过抑制细胞凋亡。

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.