多不饱和脂肪酸ω-3和ω-6影响胃癌新生血管的机制  

Effect of polyunsaturated fatty acids ω-3 and ω-6 on angiogenesis formation in human gastric cancer

作　　者：马家驰[1] 马云涛[2] 郭天康[1] 陈泉[1] 李一平[1] 苏河[1] 陈晓昌 赵晓丹[3] 郭庆金 亓建波 

机构地区：[1]甘肃省人民医院普通外科,兰州730000 [2]甘肃省人民医院中西医结合急腹症中心,兰州730000 [3]宁夏医科大学临床学院研究生院,银川750004

出　　处：《中华胃肠外科杂志》2017年第1期84-89,共6页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金资助项目（81260325）

摘　　要：目的 探讨多不饱和脂肪酸（PUFA）ω-3（二十碳五烯酸）和ω-6（花生四烯酸）及其代谢产物前列腺素（PG） E2和PGE3对胃癌新生血管的影响及作用机制。方法 分别采用细胞增殖实验、侵袭实验和体外胃癌新生血管实验检测ω-3和ω-6对人胎儿脐静脉血管内皮细胞（HUVEC）增殖、侵袭以及血管新生的影响。所有实验均设置未添加ω-3或ω-6的组别作为对照组。结果 当ω-6浓度从1 μmol/L增加到10 μmol/L, HUVEC增殖能力增加，侵袭细胞数从（28.2 ± 3.0）个增加到（32.8 ± 2.1）个，高于对照组（21.2 ± 3.2）个，差异有统计学意义（均P 〈 0.05）；而当ω-3浓度从1 μmol/L增加到10 μmol/L, HUVEC细胞增殖能力则受到抑制，侵袭细胞数从（15.8 ± 2.0）个下降到（11.0 ± 2.1）个，低于对照组（22.1 ± 3.0）个；差异有统计学意义（均P 〈 0.05）。与对照组新生血管标准量（43 721 ± 4 654）相比，ω-6对新生血管具有促进作用（1 μmol/L组：63 238±4 795；10 μmol/L组：78 166 ± 6 123），而ω-3对新生血管具有明显的抑制作用（1 μmol/L组：30 129 ± 3 102；10 μmol/L组：20 012 ± 1 541）；差异均有统计学意义（均P 〈0.01）。当ω-6中间代谢产物PGE2的浓度从1 μg/ml增加到10 μg/ml, HUVEC的增殖能力和侵袭能力均显著增加（均P 〈 0.05）；而当ω-3中间代谢产物PGE3的浓度从1 μg/ml增加到10 μg/ml时，HUVEC的增殖能力和侵袭能力则均明显受抑（均P 〈 0.05）。用罗非昔布（rofecoxib）抑制COX-2表达后，PGE2的表达水平明显下降，该抑制作用具有剂量依赖性。在表达COX-2的培养系统中，加入ω-6能促进胃癌新生血管生成（P 〈 0.01），加入ω-3则明显抑制胃癌新生血管生成（P 〈 0.01）；而在不表达COX-2的培养系统中，加入ω-6对胃癌新生血管无明显作用，加入ω-3能抑制胃癌新生血管（P 〈 0.05）。结论 ω-6PUFA可以通过血管内皮�Objective To investigate the effects of polyunsaturated fatty acids （PUFA） ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.Methods The effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell （HUVEC） were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.Results With the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2 ± 3.0 to 32.8 ± 2.1, which was higher than control group （21.2 ± 3.2） respectively （both P 〈 0.05）. With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8 ± 2.0 to 11.0 ± 2.1, which was lower than control group （22.1 ± 3.0） respectively （both P 〈 0.05）. In the angiogenesis assay, compared with control group （standard number： 43 721 ± 4 654） , the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner （1 μmol/L group： 63 238 ± 4 795, 10 μmol/L group： 78 166 ± 6 123, all P 〈 0.01）. Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129 ± 3 102 to 20 012 ± 1 541 （all P 〈 0.01）. The proliferation and migration ability of HUVECs were significantly promoted byω-6 metabolites PGE2 （P 〈 0.05） in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner （all P 〈 0.05）. After rofecoxib （a COX-

关 键 词：多不饱和脂肪酸 血管内皮细胞 新生血管 胃肿瘤 

分 类 号：R735.2[医药卫生—肿瘤]