Cancer and Lipids - The Effects and Mechanisms of Lipids on Carcinogenesis, Growth and Metastasis of Cancer -

我们发现亚油酸（n-6多不饱和脂肪酸）通过增加粪胆汁酸，特别是被认为是结肠癌促进剂的石胆酸，对偶氮氧甲烷诱导的结肠癌有促进作用。另一方面，EPA （n-3多不饱和脂肪酸）通过抑制前列腺素E_2的过量产生而对结肠癌的发生有抑制作用，而前列腺素E_2的过量产生可能伴随着肿瘤的形成。此外，EPA对n -亚硝基-n -甲基脲诱导的乳腺癌发生和植移植性Lewis肺癌（3LL）的原发肿瘤生长和肺转移也有抑制作用。为了揭示其潜在的机制，我们研究了EPA对乳腺肿瘤中前列腺素代谢的影响，2)鸟氨酸脱羧酶（ODC）活性和胆汁酸代谢对结肠癌发生的影响，3)3LL肿瘤细胞中前列腺素代谢和^ 3h -胸腺嘧啶掺入的影响。结果表明,1)环保局减少生产PGF_α< 2 > 6-keto-PGF_α< 1 >,和TXB_2除了PGE_2乳腺肿瘤在结肠致癌作用显示,2)环保局ODC活动减少结肠肿瘤和粘膜和二次胆汁酸总产量的粪便在结肠致癌作用,3)环保局减少^ 3 h-thymidine合并植入3中前列腺素的产生,将肿瘤细胞相比,亚油酸和stearec酸(饱和脂肪酸)。以上结果提示，EPA通过调节脂质和前列腺素的代谢，在乳腺癌的发生和植入肿瘤的生长转移过程中发挥抑制作用。此外，EPA不仅可以通过前列腺素的合成，还可以通过改变胆汁酸的代谢来减少结肠癌的发生。

We have showed that linoleic acid (n-6 polyunsaturated fatty acid) has promoting effect on azoxymethane-induced colon carcinogenesis by increasing the fecal bile acids, especially that of lithocholic acid which is thought to be a promoter of colon carcinogenesis. On the other hand, EPA (n-3 polyunsaturated fatty acid) has inhibitory effect on colon carcinogenesis by suppressing the excessive production of prostaglandin E_2, which may be accompanied with neoplastic formation. Furthermore, EPA also has inhibitory effect on N-nitroso-N-methylurea-induced mammary carcinogenesis and primary tumor growth and lung metastasis of implanted Lewis lung carcinoma (3LL). Here, to shed light on the underlying mechanism, the effect of EPA on 1) prostaglandin metabolism in mammary tumor, 2) the ornithine decarboxylase (ODC) activity and bile acids metabolism on colon carcinogenesis and 3) prostaglandin metabolism and ^3H-thymidine incorporation in 3LL tumor cells were studied. The results showed that 1) EPA reduced the production of PGF_<2alpha> 6-keto-PGF_<1alpha>, and TXB_2 besides PGE_2 in mammary tumors as was showed in colon carcinogenesis, 2) EPA reduced ODC activity in colon tumor and mucosa as well as total and secondary bile acid output in the feces in colon carcinogenesis, 3) EPA reduced ^3H-thymidine incorporation and production of prostaglandins in implanted 3LL tumor cells when compared with linoleic acid and stearec acid (saturated fatty acid). Above findings suggest that EPA will exert its inhibitory effect by modulating lipid and prostaglandin metabolisms in mammary carcinogenesis and in the growth and metastasis of implanted tumor. Moreover, EPA will reduce the colon carcinogenesis not only by prostaglandin synthesis but changing the bile acids metabolism.