Wang Weicang, Yang Jun, Nimiya Yoshiki, Lee Kin Sing Stephen, Sanidad Katherine, Qi Weipeng, Sukamtoh Elvira, Park Yeonhwa, Liu Zhenhua, Zhang Guodong
Department of Food Science, University of Massachusetts, Amherst, MA.
Department of Entomology and Nematology, University of California, Davis, CA.
J Nutr Biochem. 2017 Oct;48:29-35. doi: 10.1016/j.jnutbio.2017.06.006. Epub 2017 Jun 21.
Many studies have shown that dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risks of colorectal cancer; however, the underlying mechanisms are not well understood. Here we used a LC-MS/MS-based lipidomics to explore the role of eicosanoid signaling in the anti-colorectal cancer effects of ω-3 PUFAs. Our results showed that dietary feeding of ω-3 PUFAs-rich diets suppressed growth of MC38 colorectal tumor, and modulated profiles of fatty acids and eicosanoid metabolites in C57BL/6 mice. Notably, we found that dietary feeding of ω-3 PUFAs significantly increased levels of epoxydocosapentaenoic acids (EDPs, metabolites of ω-3 PUFA produced by cytochrome P450 enzymes) in plasma and tumor tissue of the treated mice. We further showed that systematic treatment with EDPs (dose=0.5 mg/kg per day) suppressed MC38 tumor growth in mice, with reduced expressions of pro-oncogenic genes such as C-myc, Axin2, and C-jun in tumor tissues. Together, these results support that formation of EDPs might contribute to the anti-colorectal cancer effects of ω-3 PUFAs.
许多研究表明，饮食中摄入ω-3多不饱和脂肪酸（PUFAs）可降低患结直肠癌的风险；然而，其潜在机制尚未完全明确。在此，我们运用基于液相色谱-串联质谱（LC-MS/MS）的脂质组学技术，探究类花生酸信号传导在ω-3 PUFAs抗结直肠癌作用中的角色。我们的结果显示，给C57BL/6小鼠喂食富含ω-3 PUFAs的饮食可抑制MC38结直肠肿瘤的生长，并调节其脂肪酸和类花生酸代谢产物的谱图。值得注意的是，我们发现给处理过的小鼠喂食ω-3 PUFAs可显著提高其血浆和肿瘤组织中环氧二十碳五烯酸（EDPs，由细胞色素P450酶产生的ω-3 PUFA代谢产物）的水平。我们进一步表明，用EDPs（剂量=每天0.5 mg/kg）进行全身治疗可抑制小鼠MC38肿瘤的生长，肿瘤组织中促癌基因如C-myc、Axin2和C-jun的表达降低。综上所述，这些结果支持EDPs的形成可能有助于ω-3 PUFAs的抗结直肠癌作用。
