n-3多不饱和脂肪酸对结肠癌细胞HCT116抗增殖作用

沈妮; 张程程; 何成自菁; 王姗姗; 于海宁; 沈生荣

doi:10.13386/j.issn1002-0306.2018.14.052

n-3多不饱和脂肪酸对结肠癌细胞HCT116抗增殖作用

Growth Inhibitory Effect of n-3 Polyunsaturated Fatty Acids on Colorectal Cancer Cell HCT116

摘要

摘要: 目的:研究n-3多不饱和脂肪酸在结肠癌细胞内的代谢与转化,深入探究脂肪酸代谢调节因子LTB₄、PGE₂、LXA₄对结肠癌细胞HCT116的毒性作用。方法:选用结肠癌细胞HCT116为研究对象,采用不同浓度n-3多不饱和脂肪酸(ALA、EPA、DHA)和阳性药物5-氟尿嘧啶(以下简称5-FU)处理细胞,检测细胞存活率、细胞凋亡、细胞脂滴聚积、细胞脂肪酸组成变化,研究代谢因子LTB₄、PGE₂、LXA₄表达水平及其对细胞增殖影响。结果:ALA、EPA、DHA和5-FU对HCT116细胞的生长具有显著的抑制作用和诱导凋亡作用(p<0.05),ALA(200 μmol/L)、EPA(160 μmol/L)、DHA(120 μmol/L)诱导凋亡率分别为7.9%、21.8%、29.2%。ALA、EPA、DHA促进HCT116细胞内脂滴积聚状态,提高不饱和脂肪酸比例,降低LTB₄积累,提高LXA₄/PGE₂比率,使癌细胞趋向于抗炎状态。结论:n-3多不饱和脂肪酸(ALA、EPA、DHA)可通过促进抗炎因子LXA₄分泌,抑制促炎因子LTB₄生成,进而对HCT116细胞产生杀伤作用。

Abstract: Objective:To investigate the biotransformation of n-3 PUFAs in HCT116 cells,and the tumoricidal action of the PUFAs metabolites such as LTB₄,PGE₂,LXA₄. Methods:Experiments in vitro were conducted on HCT116 cells supplemented with different concentration of ALA,EPA,DHA and 5-fluorouracil(5-FU)and the purposes were to investigate cell viability,apoptosis,lipid droplets,fatty acid composition,formation of PGE₂,LTB₄ and LXA₄ in HCT116 cells. Effects of PGE₂,LTB₄ and LXA₄ on cell viability were investigated by MTT assay. Results:It was observed that n-3 PUFAs(ALA,EPA,DHA)and 5-FU inhibited the growth of HCT116 colorectal carcinoma cells and produced significant apoptosis induction effect. The apoptosis rate of HCT116 cell was 7.9%,21.8%,29.2% when supplemented with ALA(200 μmol/L),EPA(160 μmol/L),DHA(120 μmol/L).N-3 PUFAs-treated cells showed an increased number of lipid droplets in their cytoplasm. As expected,higher ratio of unsaturated fatty acid was noted in the ALA,EPA,DHA treated groups compared to control. ALA,DHA and EPA supplementation to HCT116 cells suppressed production of LTB₄,but enhanced the ratio of LXA₄ to PGE₂ and then caused cancer cells to become anti-inflammatory. Conclusion:The toxicity of n-3 PUFAs(ALA,EPA,DHA)on colon cancer HCT116 cells in vitro was associated with inhibiting in the production of pro-inflammatory LTB₄ and enhancing formation of anti-inflammatory LXA₄.