MK-886与塞来昔布小剂量联合对小鼠结肠癌的抑制作用  

MK-886 combined with celecoxib inhibits colon cancer in mice

作　　者：何龙英[1] 刘春英[1] 高杉[1] 舒敏[1] 

机构地区：[1]辽宁省大连市大连大学附属中山医院消化内科,辽宁省大连市116001

出　　处：《世界华人消化杂志》2014年第2期215-220,共6页World Chinese Journal of Digestology

基　　金：辽宁省科技计划基金资助项目;No.2010225036~~

摘　　要：目的:研究选择性5-脂氧合酶活化蛋白(5-lipoxygenase activating protein,FLAP)抑制剂MK-886与选择性环氧合酶-2(cyclooxygenase-2)抑制剂赛来昔布联合及最佳配比剂量对Balb/c小鼠结肠癌基因、蛋白抑制作用的影响.方法:分别用不同浓度的MK-886、塞来昔布配比联合对患结肠癌的Balb/c小鼠进行处理,运用RT-PCR方法、Western blot方法,观察血管内皮生长因子(vascular endothelial growth factor,VEGF)、细胞间黏附因子-1(intercellular adhesion molecule,ICAM-1)的RNA、DNA、蛋白表达强弱,进一步研究两种药物联合对Balb/c小鼠结肠癌组织的抑制生长、转移的作用.结果:MK-886与塞来昔布联合能有效的抑制小鼠结肠癌的生长及转移,其中MK-886与塞来昔布联合应用的最佳配比组(第5组)变化最明显;RT-PCR结果提示两种药物联合最佳配比剂量组VEGF、ICAM-1的mRNA表达最低(第5组vs对照组F=25.826、54.540,P=0.01、0.00<0.05);Western blot实验观察到小鼠结肠癌组织内VEGF、ICAM-1蛋白表达减少,两种药物联合的最佳配比剂量应用组VEGF、ICAM-1表达量最低(第5组较其他各组F=9.699、22.761,P=0.007、0.000<0.05).结论:MK-886与塞来昔布联合中最佳配比剂量比其他联合应用组更能有效抑制结肠癌.可能与抑制VEGF、ICAM-1基因及蛋白表达有关.AIM： To study whether selective 5-lipoxygenase activating protein （FLAP） inhibitor MK-886 combined with selective cyclooxygenase 2 inhibitor celecoxib has an inhibitory effect on colon cancer in mice and to determine the optimal ratio. METHODS： Different concentrations of MK-886 combined with different doses of celecoxib were used to treat Blab/c mice with colon cancer. RT-PCR and Western blot were used to detect the mRNA and protein expression of vascular endothelia growth factor （VEGF） and intercellular adhesion molecule-1 （ICAM-1）. The effects of the two drugs on colon cancer growth and metastasis were also assessed. RESULTS： MK-886 combined with celecoxib effectively inhibited the growth and metastasis of murine colon carcinoma. MK-886 and celecoxib at the optimal ratio significantly decreased VEGF and ICAM-1 mRNA and protein expression compared to the control group （mRNA： F = 25.826, 54.540, P = 0.01, 0.00; protein： F = 0.699, 22.761, P = 0.007, 0.000）. CONCLUSION： MK-886 and celecoxib at the optimal ratio can effectively inhibit colon cancer growth and metastasis possibly by inhibition of VEGF and ICAM-1 gene and protein expression.

关 键 词：MK-88 塞来昔布 BALB c小鼠结肠癌组织 VEGF ICAM-1 

分 类 号：R735.35[医药卫生—肿瘤]