Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: mediation through cyclooxygenase-independent pathways.
Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: mediation through cyclooxygenase-independent pathways.
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DOI：
10.1158/0008-5472.can-19-2362
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发表时间：
2019-10
期刊：
影响因子：
11.2
通讯作者：
M. Boudreau;K. Sohn;S. Rhee;Sam W. Lee;J. Hunt;D. Hwang
中科院分区：
文献类型：
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作者：
M. Boudreau;K. Sohn;S. Rhee;Sam W. Lee;J. Hunt;D. Hwang
饮食中的n-3多不饱和脂肪酸(PUFAs)与n-6PUFAs相比，在体外和体内都能抑制前列腺素的细胞合成和肿瘤细胞的生长。然而，n-3多不饱和脂肪酸抑制肿瘤生长的机制尚不清楚。我们研究了膳食n-3多不饱和脂肪酸是否通过抑制环氧合酶(COX)来抑制肿瘤细胞的生长。利用逆转录病毒转染和感染系统，将组成性表达的COX-1或可诱导表达的COX-2基因稳定地导入不表达COX的结肠癌细胞株HCT-116。裸鼠移植了表达具有酶活性的COX的细胞，在实验开始前给予含有红花油或鱼油的等热量饲料2周，并在移植后再喂养21天。与喂食红花油的小鼠相比，喂食鱼油的小鼠的肿瘤体积和肿瘤负担(肿瘤体积/体重)都显著减少。这种减少甚至发生在对照组小鼠身上，注射的细胞感染了没有COX-1或COX-2基因的逆转录病毒载体。表达COX基因的肿瘤细胞在裸鼠体内和软琼脂中的生长与单独表达COX载体的肿瘤细胞生长无明显差异。与亚油酸相比，N-3多不饱和脂肪酸也能抑制这些细胞的生长。N-3多不饱和脂肪酸的这种生长抑制作用不受COX-1或COX-2过表达的影响。与普遍认为的相反，这些结果表明饮食中n-3PUFAs抑制肿瘤生长是通过COX非依赖性途径介导的。
Dietary n-3 polyunsaturated fatty acids (PUFAs), as compared with n-6 PUFAs, suppress cellular production of prostaglandins and tumor cell growth both in vitro and in vivo. However, the mechanism by which n-3 PUFAs suppress tumor growth is not understood. We investigated whether the suppression of tumor cell growth by dietary n-3 PUFAs is mediated through inhibition of cyclooxygenase (COX). A colon tumor cell line, HCT-116, that does not express COX was stably transfected with the constitutively expressed COX-1 or the inducible COX-2 cDNA using a retroviral transfection and infection system. Athymic nude mice transplanted with the cells expressing enzymatically active COX were fed isocaloric diets containing either safflower oil or fish oil for 2 weeks before the start of the experiment and for an additional 21 days after transplantation. Both tumor volume and tumor burden (tumor volume/body weight) were significantly reduced in mice fed the fish oil diet as compared with safflower oil-fed mice. This reduction occurred even in control mice that received injections with cells infected with the retroviral vector without COX-1 or COX-2 cDNA. The growth of tumor cells expressing COX was not different from the growth of those transfected with the vector alone in the nude mice and in soft agar. N-3 PUFAs, as compared with linoleic acid, also inhibited the growth of these cells in culture. This growth inhibition by n-3 PUFAs was not affected by COX-1 or COX-2 overexpression. Contrary to general belief, these results indicate that the suppression of tumor growth by dietary n-3 PUFAs is mediated through COX-independent pathways.