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Cancer and lipid-lipid metabolism in carcinogenesis, tumor growth and metastasis -

癌症发生、肿瘤生长和转移中的癌症和脂质代谢 -

基本信息

批准号：
61570626
负责人：
YAMAMOTO Masakatsu
金额：
$ 1.47万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

The effects of qualitative change of dietary fatty acids on mammary and colon carcinogenesis, primary tumor growth and lung metastasis of implanted Lewis lung carcinoma were studied. Rats or mice were fed three types of semipurified diet containing 4.7% stearic acid plus 0.3% linoleic acid (saturated fatty acid group), 5% linoleic acid (n-6 polyunsaturated fatty acid, (PUFA) group), 4.7% eicosapentaenoic acid (EPA, n-3 PUFA group) plus 0.3% linoleic acid. 1. On mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats, EPA diet significantly reduced tumor incidence, tumor weight and tumor yields when compared to other diets. Phospholipid fatty acid composition showed n-3 PUFA may in part displaced with n-6 PUFA. 2. On colon carcinogenesis induced by azoxymethane in Donryu rats, EPA diet also reduced tumor incidence and tumor yields compared to linoleic acid diet. Phospholipid fatty acid composition showed colon tumor contained higher amount of archidonic acid which is precursor of prostaglandins(PG) than normal colon mucosa. However, EPA suppressed the excessive production of PGE_2, which may be accompanied with neoplastic production, whereas linoleic acid caused a marked increase in the tumor content of PGE_2 compared to normal colon mucosa. These result suggest that EPA exert its inhibitory effect on colon or mammar carcinogenesis by modulating lipid metabolism and inhibiting PGE_2 synthesis in tumor cells. 3. On the primary growth and lung metastasis of implanted Lewis lung carcinoma in C57BL/6 mice, EPA decreased tumor weight, volume and the number of metastatic lung nodules. In biological membranes EPA may affect functional specificity, including prostanoid synthesis, and membrane structure which influences permeability, fluidity and lipid-protein interactions. Including nutritional effect, further studies are needed to understand the complex involvement of EPA on cancer cells.

本文研究了膳食脂肪酸的质变对乳腺癌和结肠癌发生、种植性刘易斯肺癌原发瘤生长和肺转移的影响。分别饲喂含4.7%硬脂酸+0.3%亚油酸（饱和脂肪酸组）、5%亚油酸（n-6多不饱和脂肪酸（PUFA）组）、4.7%二十碳五烯酸（EPA，n-3 PUFA组）+0.3%亚油酸的3种半纯化饲料。1.在N-亚硝基-N-甲基脲诱导的SD大鼠乳腺癌发生中，EPA饮食与其他饮食相比显著降低肿瘤发生率、肿瘤重量和肿瘤产量。磷脂脂肪酸组成表明n-6 PUFA可部分替代n-3 PUFA。2.在由氧化偶氮甲烷诱导的东柳大鼠结肠癌发生中，与亚油酸饮食相比，EPA饮食也降低了肿瘤发生率和肿瘤产量。磷脂脂肪酸组成显示结肠癌组织中含有大量的花生四烯酸（PG的前体）。EPA抑制PGE_2的过度产生，而亚油酸则使肿瘤组织中PGE_2含量显著增加。这些结果提示EPA可能通过调节肿瘤细胞脂质代谢和抑制PGE_2的合成而发挥其抗结肠癌和乳腺癌的作用。3. EPA对C57 BL/6小鼠移植性刘易斯肺癌的原发性生长和肺转移有抑制作用，能降低肿瘤重量、体积和肺转移结节数。在生物膜中，EPA可能影响功能特异性，包括前列腺素类合成，以及影响渗透性，流动性和脂质-蛋白质相互作用的膜结构。包括营养作用，需要进一步的研究来了解EPA对癌细胞的复杂参与。