darbufelone对胃癌SGC-7901细胞裸鼠移植瘤血管生成的影响  

Effect of Darbufelone on Angiogenesis in Nude Mouse Xenograft Model Bearing SGC-7901 Gastric Cancer Cells

作　　者：徐晓萌[1] 刘纯伦[1] 谢黎[1] 

机构地区：[1]重庆医科大学附属第一医院消化内科,重庆400016

出　　处：《世界科技研究与发展》2011年第4期654-656,699,共4页World Sci-Tech R&D

基　　金：重庆市卫生局资助课题(05-2-155)

摘　　要：目的观察环氧合酶-2/5-脂氧合酶双重抑制剂darbufelone对人胃癌皮下移植瘤血管生成的影响,并初步探讨其机制。方法建立裸鼠实体瘤模型,随机分为darbufelone组和对照组,darbufelone及生理盐水分别连续灌服4周。测量肿瘤质量、体积,计算抑瘤率;免疫组化检测CD34并计算微血管密度;RT-PCR法及Western blot法分析移植瘤组织中MMP-9、VEGF的表达。结果 dar-bufelone可明显抑制裸鼠移植瘤的生长,质量抑瘤率为58.42%,体积抑瘤率为67.13%。darbufelone组的微血管密度(MVD)(15.36±0.30)明显低于对照组(29.47±0.63)(P<0.05);darbufelone组肿瘤组织中VEGF及MMP-9在基因水平及蛋白水平的表达(p<0 05)。结论 darbufelone能有效抑制裸鼠移植瘤的生长,减少移植瘤组织中VEGF及MMP-9的表达,抑制肿瘤的微血管生成,具有抗血管生成的作用。Objective：The study aimed to verify the effects of cyclooxygenase-2/5-1ipoxygenase （cox-2/5-1ox） dual inhibitor darbufelone on angiogenesis of human gastric cancer xenografts in nude mice, and to explore the mechanisms of that. Methods： The xenograft models of human gastric carcinoma was formed in nude mice with gastric cancer cell line SGC-7901. Tire mice had been randomly divided into the darbufelone （45 mg · kg^-1 · d^- 1 ）group and the control group. All the mice were given intragastric administration for 4 weeks. The tumor volume in each group was observed regularly, and the tumors were weighed for tumor growth inhibition （TGI） after the animals were sacrificed. The expression of CD34 （representing mierovessel density, MVD） was detected by immunohistochemieal method （ S-ABC kit）. The expressions of mRNA and protein of VEGF and MMP-9 in transplantation tumor were detected by RT-PCR and Western-blot. Results ： darbufelone significantly reduced the tumor weight with an inhibition rate of 58.42% as well as tumor volume with an inhibition rate of 67. 13 % for xenografts in nude mice. The MVD in darbufelone group were significantly decreased compared with that in the control group（ 15.36 ±0. 30 vs. 29. 47 ± 0. 63 ,P 〈 0. 05 ）. After treated with the COX-2/5-LOX dual inhibitor ,the mRNA and protein expression of VEGF and MMP-9 decreased comparing with that in controls （ P 〈 0. 05 ） , respectively. Conclusion： 5-1ipoxygenase/eyelooxygenase-2 dual inhibitor darbufelone showed a significantly inhibitive effect on growth, MMP-9 and VEGF expression and angiogenesis of human gastric carcinoma transplanted subcutaneously in nude mice.

关 键 词：环氧合酶-2 5-脂氧合酶 血管生成 胃癌 移植瘤 

分 类 号：R735.2[医药卫生—肿瘤]