Darbufelone对胃癌SGC-7901细胞裸鼠移植瘤生长的影响  

Effects of darbufelone on the growth of tumor xenograft with SGC-7901 gastric cancer cells in nude mouse

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：《解放军医学杂志》2011年第2期149-152,共4页Medical Journal of Chinese People's Liberation Army

基　　金：重庆市卫生局资助课题(NO05-2-155)

摘　　要：目的观察5-脂氧合酶/环氧合酶-2双重抑制剂Darbufelone对胃癌SGC7901细胞裸鼠皮下移植瘤生长的影响,并探讨其机制。方法建立裸鼠皮下实体瘤模型,随机分为Darbufelone治疗组及对照组(n=7),Darbufelone治疗组给予Darbufelone,45mg/(kg·d),连续灌服4周,对照组给予等量生理盐水。测定移植瘤体积及质量并计算抑瘤率。采用RT-PCR及免疫组织化学法检测肿瘤组织中COX-2、5-LOX、PCNA、Bcl-2及Caspase-3的表达。结果 Darbufelone对裸鼠移植瘤的生长有明显抑制作用,与对照组相比,Darbufelone治疗组体重及移植瘤体积均明显减低(P<0.05),抑瘤率为58.42%,且未见不良反应。Darbufelone治疗组COX-2、5-LOX、PCNA、Bc1-2的mRNA及蛋白表达均明显下降,Caspase-3 mRNA及蛋白表达则显著增加(P<0.05)。结论 Darbufelone可抑制体内胃癌生长,其机制与抑制肿瘤细胞增殖及诱导凋亡有关。Objective To evaluate the effect of darbufelone,a 5-lipoxygenase/cyclooxygenase-2（5-LOX/COX-2） dual inhibitor,on the growth of subcutaneous tumor xenograft of SGC-7901 gastric cancer cells and its mechanism.Methods The xenograft model of human gastric carcinoma with SGC-7901 gastric cancer cells was reproduced in nude mice.Fourteen nude mice were randomly divided into the darbufelone group and the control group（7 each）.The mice were consecutively given intragastric administration with 45mg/（kg d） darbufelone in darbufelone group,or NS in control group for 4 weeks.The tumor volume in each group was measured regularly,and the tumor growth inhibition was calculated.The xenograft,liver,kidneys,spleen and lungs of nude mice were observed pathologically after HE staining.The expressions of mRNA and protein of 5-LOX,COX-2,PCNA,Bcl-2 and caspase-3 in transplanted tumor were detected by RT-PCR and immunohistochemistry.Results Darbufelone showed significant inhibitory effects,with an inhibition ratio of 58.42%,on the growth of tumor xenograft in vivo.The volume and weight of tumor in darbufelone group decreased significantly compared with that in control group（P〈0.05）.Darbufelone inhibited the growth of tumor xenograft with no adverse effect.Immunohistochemistry and RT-PCR analyses showed that darbufelone effectively inhibited the expression of mRNA and protein of 5-LOX,COX-2,PCNA,Bcl-2,while increased the expression of caspase-3 compared with that in the control group（P〈0.05）.Conclusions Darbufelone can inhibit the growth of gastric carcinoma in vivo,the mechanism may be related to inhibition of growth of cancer cells and the induction of apoptosis.

关 键 词：环氧化酶2抑制剂 脂氧合酶抑制剂 胃肿瘤 移植 

分 类 号：R735.2[医药卫生—肿瘤]