重组Canstatin蛋白联合氟尿嘧啶治疗胰腺癌  

Efficacy of recombinant Canstatin protein plus fluorouracil in treatment of pancreatic cancer

作　　者：何小平[1] 朱人敏[1] 王震凯[1] 汪芳裕[1] 张晓华[1] 刘炯[1] 王琳[1] 

机构地区：[1]南京军区南京总医院消化内科,江苏省南京市210002

出　　处：《世界华人消化杂志》2006年第35期3353-3357,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨血管生成抑制剂Canstatin与细胞毒药物5-FU联合应用治疗胰腺癌的效果,以期探索胰腺癌治疗新途径.方法:胰腺癌SW1990细胞(1×107/只)注射到32只裸鼠皮下,建立胰腺癌皮下移植瘤模型.当肿瘤长至2-3mm时,随机分4组,即PBS(0.3mL/d)对照组、5-FU(12.5mg/(kg·d)×5d)治疗组、Canstatin(10mg/(kg·d)×3wk)治疗组、及5-FU[12.5mg/(kg·d)×5d]+Canstatin[10mg/(kg·d)×3wk)]联合治疗组,给药途径均为ip.治疗期间,定期用圆规和游标卡尺测量皮下移植瘤大小.疗程结束时,取下瘤体,常规病理切片,观察药物毒性反应,CD34免疫组化染色,检测肿瘤内微血管密度(MVD).结果:Canstatin治疗组移植瘤体积从第10天起显著小于对照组(P<0.01),5-FU治疗组第7天起就显著小于对照组(P<0.05),而联合治疗组自第3天起,移植瘤体积就显著小于对照组(P<0.05).疗程结束时,联合治疗组小鼠移植瘤体积显著小于其余各组(P<0.01),抑瘤率最高,达83.2%.治疗期间,各实验组未观察到明显毒性反应.免疫组化染色显示,Canstatin组(25.2±3.7)和联合治疗组(22.0±4.8)治疗小鼠肿瘤组织内MVD显著低于对照组(36.8±9.4)和5-FU治疗组(31.6±4.0)(P<0.05),而5-FU治疗组与对照组间无显著差异.结论:重组人Canstatin蛋白能有效抑制人胰腺癌生长,无明显副作用,作用机制是抑制肿瘤新血管形成,与细胞毒药物联合使用,具有协同作用,为胰腺癌治疗提供了新的有力的治疗方法.AIM： To study the anti-tumor effects of recombinant Canstatin protein plus 5-fluorouracil （5-FU） on pancreatic cancer in order to develop a new treatment modality. METHODS： Tumor xenografts were established by subcutaneous inoculation of 1×10^7 SW1990 pancreatic cancer cells into the right flanks of 32 BALB/c nude mice. When the tumors reached 2-3 mm in diameter, mice were randomly divided into 4 groups： phosphate buffer solution （PBS） group were treated with PBS 0.3 mL per day for 3 weeks; Canstatin group were treated with Canstatin 5 mg/kg per day for 3 weeks; 5-FU group were treated with 5-FU 12.5 mg/kg per day for 5 days; and combination group were treated with 5-FU 12.5 mg/kg per day for 5 days plus Canstatin 5 mg/kg per day for 3 weeks. All the agents were injected intraperitoneally. During the treatment period, the subcutaneous tumors were measured by compasses and caliper every 3 or 4 days. At the end of the experiment, all the tumors were resected, and both routine pathological and immunohistochemical examinations were performed to observe the drug toxicity and intratumoral microvescular density （MVD）. RESULTS： The size of tumors treated with Canstatin was significantly decreased in comparison with that of PBS group from the 10^th day after treatment （P 〈 0.01）. In 5-FU group, the tumor size was obviously smaller than that in PBS group from the 7^th day after treatment （P 〈 0.05）, and in combination group from the 3^rd day after treatment （P 〈 0.05）. At the end of the experiment, the size of tumors in combination group was the lowest （P 〈 0.05）, with the highest tumor suppression rate of 83.2%. During treatment, no obvious toxicity was observed. The immunohistochemical examination showed that the MVD in Canstatin group （25.2 ± 3.7） or combination group （22.0 ± 4.8） was significantly lower than that in PBS group （36.8 ± 9.4） or 5-FU group （31.6 ± 4.0）（P 〈 0.05）. No significant difference was found in MVD between 5-FU and PBS group.

关 键 词：胰腺癌 血管生成 Canstatin蛋白 氟尿嘧啶 

分 类 号：R735.9[医药卫生—肿瘤]