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

点击翻译按钮获取中文摘要

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.