ω-3多不饱和脂肪酸对人胃癌细胞系生长的抑制作用及其机制

Inhibitory effect of ω-3 polyunsaturated fatty acids on the growth of human gastric cancer cell lines

目的探讨ω-3多不饱和脂肪酸(ω-3PUFA)对人胃癌细胞系生长的抑制作用及其机制。方法采用四甲基偶氮唑蓝实验、细胞形态学观察、片断DNA电泳、流式细胞技术和硫代巴比妥酸法对细胞增殖、细胞凋亡以及细胞内脂质过氧化产物丙二醛(MDA)含量进行分析。结果胃癌细胞经40μg/ml的二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)作用24～72h后,细胞增殖受到明显抑制,同时诱发细胞凋亡,且呈现时间依赖关系。凋亡细胞表现为细胞固缩、胞膜突起出泡、核染色质凝聚、边集和凋亡小体形成。DNA裂解片断呈典型的凋亡“阶梯”状条带,流式细胞仪见明显的亚二倍体峰。EPA和DHA作用72h,胃癌细胞内MDA的含量显著高于对照组(P<0.001)。EPA和DHA对正常成纤维细胞的增殖和脂质过氧化反应无明显影响。结论ω-3PUFA通过抑制细胞增殖和诱导细胞凋亡来阻遏胃癌细胞的生长,这种作用可能与细胞内脂质过氧化产物的增加有关。

Objective To investigate the inhibitory effect and mechanism of ω 3PUFA on the growth of human gastric cancer cell lines. Methods Human gastric cancer cell lines SGC 7901, MGC 803 and fibroblast cell line HLF were treated with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The inhibition of cell proliferation and induction of apoptosis were evaluated by MTT assay, cell morphology, DNA gel electrophoresis and flow cytometric DNA analysis. Intracellular lipid peroxidation production malonaldehyde (MDA) was measured by thibabituric acid assay. Results After incubation of gastric cancer cells with 40 μg/ml EPA or DHA for 24 h to 72 h, the cell proliferation was reduced and apoptosis was promoted in a time dependent manner. The morphological changes of apoptotic cells were characterized by cell shrinkage, membrane blebing, chromatin condensation, and formation of apoptotic bodies. The gel electrophoresis of DNA degradation displayed typical DNA ladder fragments. Flow cytometric analysis showed subdiploid peak in apoptotic cells. Intracellular MDA content siginificantly increased in gastric cancer cells treated with EPA or DHA at 72 h compared with that in control group(P< 0.001). There was little effect of EPA and DHA on the cell proliferation and lipid peroxidation in normal fibroblast cells. Conclusions ω 3PUFA can inhibit the growth of gastric cancer cells via reducing cell proliferation and inducing apoptosis. These effects may be associated with the increase of lipid peroxidation production.