比利时鲁汶大学Olivier Feron研究团队发现，酸性肿瘤环境中n-3和n-6多不饱和脂肪酸的过氧化导致铁死亡介导的抗癌作用。相关论文于2021年6月11日在线发表在《细胞—代谢》杂志上。

研究人员表示，肿瘤酸中毒通过刺激癌细胞中的脂肪酸（FA）代谢促进疾病进展。但研究人员没有阻止酸性癌细胞对FA的使用，而是检查了特定FA的过量摄取是否会导致抗肿瘤作用。结果表明，在环境酸中毒条件下，n-3和n-6多不饱和脂肪酸（PUFA）选择性地诱导癌细胞中的铁死亡。在超过甘油三酯储存到脂滴中的缓冲能力后，n-3和n-6 PUFA过氧化导致细胞毒性作用，在二酰基甘油酰基转移酶抑制剂 （DGATi）存在下更是如此。

最后，与富含单不饱和脂肪酸的饮食相比，富含n-3长链PUFA的饮食显著延迟了小鼠肿瘤的生长，这种效果通过施用DGATi或铁死亡诱导剂进一步增强。这些数据指出膳食PUFA可作为一种选择性辅助抗肿瘤方式来有效地补充药理学方法。

附：英文原文

Title: Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects

Author: Emeline Dierge, Elena Debock, Céline Guilbaud, Cyril Corbet, Eric Mignolet, Louise Mignard, Estelle Bastien, Chantal Dessy, Yvan Larondelle, Olivier Feron

Issue&Volume: 2021-06-11

Abstract: Tumor acidosis promotes disease progression through a stimulation of fatty acid (FA)metabolism in cancer cells. Instead of blocking the use of FAs by acidic cancer cells,we examined whether excess uptake of specific FAs could lead to antitumor effects.We found that n-3 but also remarkably n-6 polyunsaturated FA (PUFA) selectively inducedferroptosis in cancer cells under ambient acidosis. Upon exceeding buffering capacityof triglyceride storage into lipid droplets, n-3 and n-6 PUFA peroxidation led tocytotoxic effects in proportion to the number of double bonds and even more so inthe presence of diacylglycerol acyltransferase inhibitors (DGATi). Finally, an n-3long-chain PUFA-rich diet significantly delayed mouse tumor growth when compared witha monounsaturated FA-rich diet, an effect further accentuated by administration ofDGATi or ferroptosis inducers. These data point out dietary PUFA as a selective adjuvantantitumor modality that may efficiently complement pharmacological approaches.

DOI: 10.1016/j.cmet.2021.05.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00233-3