Huang Qionglin, Wen Juan, Chen Guangzhao, Ge Miaomiao, Gao Yihua, Ye Xiaoxia, Liu Chunan, Cai Chun
a Analysis Center, Guangdong Medical University , Zhanjiang , China.
Nutr Cancer. 2016;68(1):113-9. doi: 10.1080/01635581.2016.1115526. Epub 2016 Jan 15.
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.
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。