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ω-3多不饱和脂肪酸通过防止结直肠癌大鼠基因组DNA甲基化降低来抑制肿瘤生长。

Omega-3 Polyunsaturated Fatty Acids Inhibited Tumor Growth via Preventing the Decrease of Genomic DNA Methylation in Colorectal Cancer Rats.

作者信息

Huang Qionglin, Wen Juan, Chen Guangzhao, Ge Miaomiao, Gao Yihua, Ye Xiaoxia, Liu Chunan, Cai Chun

机构信息

a Analysis Center, Guangdong Medical University , Zhanjiang , China.

出版信息

Nutr Cancer. 2016;68(1):113-9. doi: 10.1080/01635581.2016.1115526. Epub 2016 Jan 15.

Abstract

Omge-3 polyunsaturated fatty acids (PUFAs) exhibited significant effect in inhibiting various tumors. However, the mechanisms of its anticancer role have not been fully demonstrated. The declination of 5-methylcytosine (5 mC) was closely associated with poor prognosis of tumors. To explore whether omega-3 PUFAs influences on DNA methylation level in tumors, colorectal cancer (CRC) rat model were constructed using N-methyl phosphite nitrourea and omega-3 PUFAs were fed to part of the rats during tumor induction. The PUFAs contents in the rats of 3 experimental groups were measured using gas chromatography and 5 mC level were detected by liquid chromatography tandem mass spectrometry. The results showed that tumor incidence in omega-3 treated rats was much lower than in CRC model rats, which confirmed significant antitumor role of omega-3 PUFAs. Six PUFA members categorized to omega-3 and omega-6 families were quantified and the ratio of omega-6/omega-3 PUFAs was remarkably lower in omega-3 PUFAs treatment group than in CRC model group. 5 mC content in omega-3 PUFAs treated rats was higher than in CRC model rats, suggesting omega-3 PUFAs promoted 5 mC synthesis. Therefore, omega-3 PUFAs probably inhibited tumor growth via regulating DNA methylation process, which provided a novel anticancer mechanism of omega-3 PUFAs from epigenetic view.

摘要

ω-3多不饱和脂肪酸(PUFAs)在抑制多种肿瘤方面表现出显著效果。然而,其抗癌作用的机制尚未得到充分证明。5-甲基胞嘧啶(5mC)水平的下降与肿瘤的不良预后密切相关。为了探究ω-3 PUFAs是否影响肿瘤中的DNA甲基化水平,使用亚硝基甲基膦酸脲构建了大鼠结直肠癌(CRC)模型,并在肿瘤诱导过程中对部分大鼠喂食ω-3 PUFAs。采用气相色谱法测定3个实验组大鼠的PUFAs含量,通过液相色谱串联质谱法检测5mC水平。结果显示,ω-3处理组大鼠的肿瘤发生率远低于CRC模型大鼠,这证实了ω-3 PUFAs具有显著的抗肿瘤作用。对归类于ω-3和ω-6家族的6种PUFA成员进行了定量分析,结果表明ω-3 PUFAs处理组中ω-6/ω-3 PUFAs的比例显著低于CRC模型组。ω-3 PUFAs处理组大鼠的5mC含量高于CRC模型大鼠,表明ω-3 PUFAs促进了5mC的合成。因此,ω-3 PUFAs可能通过调节DNA甲基化过程来抑制肿瘤生长,这从表观遗传学角度为ω-3 PUFAs提供了一种新的抗癌机制。

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