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

癌症与脂质 - 脂质对癌症发生、生长和转移的影响和机制 -

基本信息

批准号：
01570727
负责人：
YAMAMOTO Masakatsu
金额：
$ 1.28万
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：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

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.

我们已经表明，亚油酸（n-6多不饱和脂肪酸）通过增加粪便胆汁酸，特别是石胆酸（被认为是结肠癌发生的促进剂），对氧化偶氮甲烷诱导的结肠癌发生具有促进作用。另一方面，EPA（n-3多不饱和脂肪酸）通过抑制前列腺素E_2的过度生成而对结肠癌的发生具有抑制作用。此外，EPA对N-亚硝基-N-甲基脲诱导的乳腺癌的发生和种植性刘易斯肺癌（3LL）的原发肿瘤生长和肺转移也有抑制作用。在此，为了阐明其潜在机制，研究了EPA对1）乳腺肿瘤中前列腺素代谢的影响，2）结肠癌发生过程中鸟氨酸脱羧酶（ODC）活性和胆汁酸代谢的影响，以及3）3LL肿瘤细胞中前列腺素代谢和^3H-胸苷掺入的影响。结果表明：（1）EPA可减少乳腺肿瘤中PGF_<2alpha>6-keto-PGF_<1alpha>2和TXB_2的产生，与结肠癌发生过程中的PGE_2一样;（2）EPA可减少结肠癌发生过程中结肠肿瘤和粘膜中ODC的活性以及粪便中总胆汁酸和次级胆汁酸的排出;（3）与亚油酸和硬脂酸（饱和脂肪酸）相比，EPA可减少植入的3LL肿瘤细胞中^3H-胸苷的掺入和三尖杉酯碱的产生。以上结果提示，EPA可能通过调节脂质和前列腺素代谢而发挥其抑制乳腺癌发生及移植瘤生长和转移的作用。此外，EPA不仅通过前列腺素的合成，而且通过改变胆汁酸的代谢来减少结肠癌的发生。