塞来昔布联合替吉奥对胃癌裸鼠移植瘤生长及淋巴管生成的影响  

Effect of celecoxib combined with tegafur,gimeracil and oteracil potassium on growth and lymphangiogenesis of the xenograft tumor of gastric cancer in nude mice

作　　者：孟翠翠 罗治彬[2] 

机构地区：[1]苏州大学附属常州肿瘤医院放疗科,江苏常州213001 [2]重庆市第三人民医院肿瘤科,重庆400016

出　　处：《解放军医学杂志》2013年第12期967-971,共5页Medical Journal of Chinese People's Liberation Army

摘　　要：目的探讨选择性环氧化酶2抑制剂塞来昔布联合替吉奥对人胃癌裸鼠皮下移植瘤生长及淋巴管生成的影响及其可能机制。方法建立胃癌裸鼠皮下移植瘤模型,成瘤后将裸鼠随机分为4组(n=6):阴性对照组、塞来昔布组、替吉奥组、塞来昔布联合替吉奥组(联合给药组)。连续给药21d后,取材,测瘤重,计算抑瘤率及给药前后裸鼠体重变化,评价药物治疗的毒副作用。应用免疫组化方法检测各组肿瘤组织中COX-2、VEGF-C蛋白表达情况并计数淋巴管密度。结果药物治疗组裸鼠并未出现明显的不良反应,体重均较治疗前明显增加(P<0.05)。塞来昔布组、替吉奥组、联合给药组的抑瘤率分别为32.71%、48.13%、79.44%。塞来昔布组、联合给药组COX-2、VEGF-C表达及淋巴管密度明显低于对照组、替吉奥组(P<0.05),替吉奥组COX-2、VEGF-C表达及淋巴管密度与对照组比较差异无统计学意义(P>0.05)。结论塞来昔布、替吉奥单独作用均可明显抑制肿瘤生长,且二者应用具有协同抑瘤作用。塞来昔布单用或联合替吉奥均可通过下调COX-2表达、进而下调VEGF-C的表达而抑制肿瘤组织淋巴管生成。Objective To investigate the effect and analyze the possible mechanism of celecoxib combined with tegafur, gimeracil and oteracil potassium on growth and lymphangiogenesis of subcutaneously transplanted human gastric cancer in nude mice. Methods Human gastric cancer was transplanted subcutaneously successfully in nude mice. When the largest diameter of tumor reached about 5mm, the nude mice were randomly divided into four groups （6 each）： control group, celecoxib group, tegafur＋gimeracil＋oteracil potassium group, and celecoxib combination group. The drugs were administered respectively for 21 days. Then the tumor tissues were collected, tumor weight was measured, and tumor inhibition rate was calculated. The changes in body weight of the nude mice before and after treatment were recorded, and the side effect of drug therapy was assessed. The expression levels of COX-2 and VEGF-C protein were determined by immunohistochemistry, and the density of lymphatic vessel was calculated. Results No obvious side effect was found, and the body weight increased after the treatment （P〈0.05） in nude mice except those in control group. The tumor inhibition rates of celecoxib group, tegafur＋gimeracil＋oteracil potassium group and combination group were 32.71%, 48.13% and 79.44%, respectively. The expressions of COX-2 and VEGF-C protein and the lymphatic vessel density were found to be decreased in celecoxib group and combination group compared with that in control group and tegafur＋gimeracil＋oteracil potassium group （]9〈0.05）, but no significant difference was found between tegafur＋gimeracil＋oteracil potassium group and control group （P〉0.05）. Conclusion When given alone, both celecoxib and tegafur＋gimeracil＋oteracil potassium show obvious antitumor effect, and combination of these two drugs will give rise a synergistical antitumor effect. Celecoxib and celecoxib combined with tegafur gimeracil oteracil potassium may reduce the expression of COX-2, in turn downregulate the expression of

关 键 词：塞来昔布 替吉奥 环氧化酶2抑制剂 血管内皮生长因子C 淋巴管生成 

分 类 号：R73[医药卫生—肿瘤]