Carcinogenesis：鱼油生物活性成分DHA抗乳腺癌

近年来已有文献指出适当的营养补充可有效帮助癌症患者，其中又以鱼油最受到注目。鱼油中内含许多ω3多元不饱和脂肪酸，包括docosahexaenoic acid (DHA) （十二碳六烯酸）。

越来越多的证据表明鱼油对体外细胞水平和动物模型中乳腺癌的生长和侵袭有抑制作用。乳腺癌细胞所表达的CSF-1（细胞集落刺激因子1）是恶性肿瘤转移强有力的激活因子。近日Carcinogenesis杂志刊登的一则研究报告中，研究人员用两个人源乳腺癌细胞株MDA-MB-231和MCF-7证实，鱼油的生物活性成分DHA（十二碳六烯酸）能抑制这些癌细胞CSF-1的表达，同时也能抑制其分泌。

研究人员发现肿瘤抑制蛋白PTEN通过PI3激酶/Akt信号通路的转录机制调节CSF-1的表达。有趣的是，DHA能显著抑制miR-21的表达。此外，miR-21-诱导CSF-1基因mRNA表达水平上调，其转录水平的上调能被和miR-21识别序列以及缺乏3'UTR的PTEN基因所阻止。

引人注目的是，miR-21能逆转DHA减少CSF-1表达和分泌的功效。最后，研究数据显示 miR-21以及CSF-1的表达在给予补充鱼油的饮食小鼠的乳腺肿瘤组织中明显减弱。研究结果揭示了鱼油饮食阻断miR-21，从而增加PTEN的水平，能防止CSF-1在乳腺癌中的表达发挥抗肿瘤作用。

doi:10.1093/carcin/bgs198
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miR-21 is Targeted By Omega-3 Polyunsaturated Fatty Acid to Regulate Breast Tumor CSF-1 Expression.

Mandal CC, Ghosh-Choudhury T, Dey N, Ghosh Choudhury G, Ghosh-Choudhury N.

Increasing evidence show the beneficial effects of fish oil on breast cancer growth and invasion in vitro and in animal models. Expression of CSF-1 (colony stimulating factor-1) by breast cancer cells acts as potent activator of malignancy and metastasis. In this report, we used two human breast cancer cell lines MDA-MB-231 and MCF-7 to show that the bioactive fish oil component DHA (docosahexaenoic acid) inhibits expression of CSF-1 and its secretion from these cancer cells. We found that the tumor suppressor protein PTEN regulates CSF-1 expression through PI 3 kinase/Akt signaling via a transcriptional mechanism. The enhanced abundance of microRNA-21 (miR-21) in breast cancer cells contributes to the growth and metastasis. Interestingly, DHA significantly inhibited expression of miR-21. miR-21 Sponge, which derepresses the miR-21 targets, markedly decreased expression of CSF-1 and its secretion. Furthermore, miR-21-induced upregulation of CSF-1 mRNA and its transcription were prevented by expression of PTEN mRNA lacking 3' UTR and miR-21 recognition sequence. Strikingly, miR-21 reversed DHA-forced reduction of CSF-1 expression and secretion. Finally, we found that expression of miR-21 as well as CSF-1 were significantly attenuated in breast tumors of mice receiving a diet supplemented with fish oil. Our results reveal a novel mechanism for the therapeutic function of fish oil diet which blocks miR-21; thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer.