Clarify the mechanism of colon carcinogenesis by fat intake

阐明脂肪摄入导致结肠癌的机制

• 批准号: 18590691
• 负责人: IWAKIRI Ryuichi
• 金额: $ 2.43万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590691/
• 关键词: Colon cancer; azoxymethane; free fatty acid; aberrant crypt foci; conjugated linoleic acid; triglyiceride; グルタチオン; 共役リノール酸; aberrant crypt foci; 飽和脂肪酸; 不飽和脂肪酸

The aim of this study is to investigate the effect of conjugated linoleic acid (CLA) on colon carcinogenesis in rats fed with a high fat diet. Materials and Methods: Fifteen mg/kg body weight of azoxymethane (AOM) was i.p injected to male SD rats once a week for 2 weeks. Rats were fed with 10% beef tallow as a basal diet or supplemented with 1% CLA free fatty acid type (FFA) and triglyceride type (TG). Colonic aberrant crypt foci (ACF) was examined at 12 weeks. Colon cancer was examined at 44 weeks. Lipid peroxide level in serum was evaluated by thiobarbituric acid-reactive substance. Superoxide dismutase (SOD) activity was by WST-1 method. Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) were by EIA. Colon proliferation was evaluated by BrdU uptake. Results: Both of CLA types decreased the number of ACFs and colon cancer incidence. CLA decreased BrdU uptake and expression of PGE2 and TXB2 in colonic mucosa. In rats fed with CLA without AOM, more BrdU uptook cells presented in lower area of crypt. Without CLA, more BrdU uptook cells presented in middle. Only FFA decreased oxidative stress. Conclusion: Despite long term feeding of a high fat diet, ingested CLA especially FFA was suggested to suppress colon carcinogenesis via arachidonate cascade. Decreasing and lower localization of BrdU uptook cells with CLA indicated that CLA itself played an important role in colon carcinogenicity. Furthermore, FFA was suggested to have higher efficacy than TG by decreasing oxidative stress.

本研究旨在探讨共轭亚油酸（CLA）对高脂饮食大鼠结肠癌发生的影响。材料与方法：雄性SD大鼠腹腔注射氧化偶氮甲烷（AOM）15 mg/kg体重，每周1次，连续2周。以10%牛脂为基础饲料，或添加1% CLA游离脂肪酸型（FFA）和甘油三酯型（TG）饲料。12周时检查结肠异常隐窝病灶（ACF）。在44周时检查结肠癌。用硫代巴比妥酸反应物法测定血清脂质过氧化物水平。超氧化物歧化酶（SOD）活性测定采用WST-1法。酶免疫法测定前列腺素E2（PGE 2）、血栓素B2（TXB 2）。结肠增殖通过BrdU摄取来评价。结果：两种CLA均可降低ACFs的数量和结肠癌的发生率。CLA可降低结肠粘膜对BrdU的摄取和PGE 2、TXB 2的表达。CLA组大鼠腺窝下部BrdU摄取细胞增多。不加CLA时，BrdU摄取细胞多集中在中部。只有FFA降低氧化应激。结论：尽管长期喂食高脂饮食，但摄入CLA特别是FFA被认为通过花生四烯酸级联反应抑制结肠癌的发生。CLA对BrdU摄取细胞的抑制和定位降低表明CLA本身在结肠致癌性中起重要作用。此外，FFA通过降低氧化应激而具有比TG更高的功效。

项目成果

Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro.

• DOI: 10.1152/ajpgi.00145.2006
• 发表时间: 2007-03
• 期刊: American journal of physiology. Gastrointestinal and liver physiology
• 作者: S. Amemori;A. Ootani;S. Aoki;T. Fujise;R. Shimoda;T. Kakimoto;Ryosuke Shiraishi;Y. Sakata

T-cell deficiency responses to liver carcinogenesis in rats.

T 细胞缺陷对大鼠肝癌发生的反应。

• 发表时间: 2006
• 期刊: J. Exp. Biol. 231
• 作者: Fujise;T.;Iwakiri;R.;Wu;B.;Amemori;S.;Kakimoto;T.;Yokoyama;F.;Sakata;Y.;Tsunada;S.;Fujimoto;K;Iwakiri R;Fujise T;Wu B
• 通讯作者: Wu B

Suppression of intestinal mucosal apoptosis by ghrelin in fasted rats.

胃饥饿素对禁食大鼠肠粘膜细胞凋亡的抑制作用。

• 发表时间: 2008
• 期刊: Exp Biol Med 233
• 作者: Park JM;Kakimoto T;Kuroki T;Shiraishi R;Fujise T;Iwakiri R;Fujimoto K.
• 通讯作者: Fujimoto K.

Mechanism of colon carcinogenesis induced by dietary fatty acid and accelerating Wnt signaling

膳食脂肪酸和加速Wnt信号传导诱导结肠癌的机制

• 发表时间: 2007
• 作者: Shiraishi R;et. al.
• 通讯作者: et. al.

Differentiation of Gastric Surface Mucous Cells(GSM06) Induced by Air Liquid Interface Is Regulated Partly through Mitogen-Activated Protein Kinase Pathway

气液界面诱导的胃表面粘液细胞（GSM06）的分化部分通过丝裂原激活蛋白激酶途径调节

• 发表时间: 2007
• 期刊: J. Gastroenterol. Hepatol 22
• 作者: Yokoyama;F.;Sakata;Y.;Ootani;A.;Fujise;T.;Kakimoto;T.;Amemori;S.;Kuroki;T.;Tsunada;S.;Iwakiri;R.;Fujimoto;K
• 通讯作者: K