Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth
Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth
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DOI：
10.1097/mpa.0b013e31815ccc44
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发表时间：
2008-05-01
期刊：
影响因子：
2.9
通讯作者：
Eibl, Guido
中科院分区：
文献类型：
--
作者：
Funahashi, Hitoshi;Satake, Makoto;Eibl, Guido
目的：流行病学研究表明，富含 n-3 多不饱和脂肪酸 (PUFA) 的鱼油具有抗肿瘤活性，而 n-6 PUFA 可能会刺激癌症的发展。本研究的目的是评估n-6和n-3 PUFA对胰腺癌生长的影响。方法：n-6 PUFA花生四烯酸（AA）刺激环氧合酶（COX）2阳性人胰腺癌（PaCa）细胞的生长，这是由COX-2产生的前列腺素E-2（PGE（2））与EP2和EP4受体结合介导的。相反，n-3 PUFA二十碳五烯酸降低了COX-2阳性和COX-2阴性PaCa细胞的生长。二十碳五烯酸的 COX-2 依赖性机制是通过 PGE(3) 与 EP2 和 EP4 受体的结合介导的。饮食中摄入 n-3 PUFA 可降低异种移植模型中胰腺癌的生长，同时伴随肿瘤中 PGE(2) 的减少和 PGE(3) 的增加。结论：我们的研究提供证据表明 n-3 PUFA 具有抗肿瘤活性，而 n-6 PUFA 则刺激胰腺肿瘤生长。 n-3 和 n-6 PUFA 的相反作用是通过不同前列腺素种类的形成介导的。 n-3 PUFA 作为单一疗法或与标准化疗药物的联合疗法可能对胰腺癌患者有益。
Objectives: Epidemiologic studies suggest that fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), possesses antitumor activity, whereas n-6 PUFAs may stimulate the development of cancers. The aim of this study was to evaluate the effects of n-6 and n-3 PUFAs on the growth of pancreatic cancer.Methods: The n-6 PUFA arachidonic acid (AA) stimulated the growth of cyclooxygenase (COX) 2 positive human pancreatic cancer (PaCa) cells, which was mediated by COX-2 generated prostaglandin E-2 (PGE(2)) binding to EP2 and EP4 receptors. In contrast, the n-3 PUFA eicosapentaenoic acid decreased the growth of COX-2-positive and COX-2-negative PaCa cells. The COX-2-dependent mechanism of eicosapentaenoic acid was mediated by binding of PGE(3) to EP2 and EP4 receptors. Dietary intake of n-3 PUFAs decreased the growth of pancreatic cancers in a xenograft model, which was accompanied by a decrease of PGE(2) and an increase of PGE(3) in the tumors.Conclusions: Our studies provide evidence that n-3 PUFAs possess antitumor activities, whereas n-6 PUFAs stimulate pancreatic tumor growth. The opposite effects of n-3 and n-6 PUFAs are mediated by the formation of different prostaglandin species. n-3 PUFAs may prove beneficial as monotherapy or combination therapy with standard chemotherapeutic agents in pancreatic cancer patients.