High susceptibility to azoxymethane-induced colorectal carcinogenesis in obese KK-Ay mice
High susceptibility to azoxymethane-induced colorectal carcinogenesis in obese KK-Ay mice
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DOI：
10.1002/ijc.25711
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发表时间：
2011-08-01
影响因子：
6.4
通讯作者：
Wakabayashi, Keiji
中科院分区：
文献类型：
--
作者：
Teraoka, Naoya;Mutoh, Michihiro;Wakabayashi, Keiji
肥胖与结肠癌发生有关。然而，没有太多的信息是关于肥胖相关的结直肠癌的机制，只有几个有用的动物模型研究肥胖和结直肠癌之间的潜在机制。KK-A（y）小鼠表现出严重肥胖。通过显微计算机断层扫描评估的内脏脂肪量几乎是同龄C57 BL/6 J小鼠的15倍。用氧化偶氮甲烷（AOM; 200 μ g/小鼠，每周注射一次，共3次）处理导致KK-A（y）小鼠中结肠异常隐窝病灶（ACF）发育（约70 ACF/小鼠）与瘦型C57 BL/6 J小鼠（约9 ACF/小鼠）相比显著增加。此外，以200 μ g/小鼠的剂量每周一次给药6次AOM，仅在最后一次AOM注射后7周内就发生了结肠直肠腺癌。KK-A（y）小鼠的腺癌发生率为88%，明显高于C57 BL/6 J小鼠中观察到的4%。KK-A（y）小鼠的肿瘤数为7.80/只，也明显高于C57 BL/6 J小鼠的0.12/只。有趣的是，在大多数AOM处理的KK-A（y）小鼠中观察到腺癌沿着显著的肿瘤血管生成，并且一些显示粘膜下侵袭。这些结果表明，KK-A（y）小鼠，具有完整的瘦素和瘦素受体Ob-Rbl，可能是一个有用的动物模型，以研究肥胖相关的癌症。
Obesity is associated with colon carcinogenesis. However, not much information is available regarding the mechanisms of obesity-associated colorectal cancer, and there are only few useful animal models for investigating the underlying mechanism between obesity and colorectal cancer. KK-A(y) mice exhibit severe obesity. Amount of visceral fat assessed by micro-computed tomography was almost 15 times higher than that of same aged C57BL/6J mice. Treatment with azoxymethane (AOM; 200 mu g/mouse injected once a week for 3 times) resulted in markedly increased colon aberrant crypt foci (ACF) development (approximate to 70 ACF/mouse) in KK-A(y) mice compared with lean C57BL/6J mice (approximate to 9 ACF/mouse). Moreover, administration of AOM at a dose of 200 mu g/mouse once a week for 6 times developed colorectal adenocarcinomas within only 7 weeks after the last AOM injection. The incidence of adenocarcinoma was 88% in KK-A(y) mice and was markedly higher than the 4% observed in C57BL/6J mice. The number of tumors/mouse was 7.80 in KK-A(y) mice and also markedly higher than the 0.12 in the C57BL/6J case. Interestingly, adenocarcinomas were observed in most of the AOM-treated KK-A(y) mice along with remarkable tumor angiogenesis, and some showed submucosal invasion. These results indicate that the KK-A(y) mouse, featuring intact leptin and leptin receptor Ob-Rbl, could be a useful animal model to investigate obesity-associated cancer.