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

研究了膳食脂肪酸质变对植入式Lewis肺癌发生、原发肿瘤生长及肺转移的影响。大鼠或小鼠分别饲喂硬脂酸+ 0.3%亚油酸（饱和脂肪酸组）、5%亚油酸（n-6多不饱和脂肪酸组）、4.7%二十碳五烯酸（EPA， n-3 PUFA组）+ 0.3%亚油酸的三种半纯化饲料。1. 在n -亚硝基-n -甲基脲诱导的Sprague-Dawley大鼠乳腺癌中，EPA日粮与其他日粮相比，显著降低肿瘤发生率、肿瘤重量和肿瘤产量。磷脂脂肪酸组成显示n-3 PUFA可能部分被n-6 PUFA取代。2. 在氮氧甲烷诱导的东流大鼠结肠癌中，EPA饮食与亚油酸饮食相比，还能降低肿瘤发生率和肿瘤产量。磷脂脂肪酸组成显示结肠肿瘤中前列腺素（PG）前体阿齐酮酸的含量高于正常结肠粘膜。然而，EPA抑制了PGE_2的过量产生，这可能伴随着肿瘤的产生，而亚油酸导致肿瘤中PGE_2的含量明显高于正常结肠粘膜。提示EPA通过调节肿瘤细胞脂质代谢和抑制PGE_2合成来抑制结肠癌或乳腺癌的发生。3. 对C57BL/6小鼠移植性Lewis肺癌的原发生长和肺转移，EPA降低肿瘤的重量、体积和转移性肺结节的数量。在生物膜中，EPA可能影响功能特异性，包括前列腺素合成和膜结构，从而影响渗透性、流动性和脂质-蛋白相互作用。包括营养作用在内，还需要进一步的研究来了解EPA对癌细胞的复杂作用。

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.