重组人内皮抑素联合紫杉醇+顺铂化疗方案治疗人乳腺癌祼鼠移植瘤的研究  

Recombinant human endostatin combined with paclitaxel-cisplatin chemotherapy in treatment of human breast cancer xenograft in nude mice

作　　者：邓莉[1] 张轩珍[2] 王卫东[1] 陈正堂[1] 曹正怀[1] 

机构地区：[1]第三军医大学新桥医院全军肿瘤诊治研究所,重庆400037 [2]重庆市妇幼保健院病理科,重庆400013

出　　处：《第三军医大学学报》2008年第9期783-786,共4页Journal of Third Military Medical University

基　　金：全军医学科研“十一五”计划科技攻关项目(06G069)~~

摘　　要：目的探讨重组人内皮抑素(endostar,商品名恩度)联合化疗方案对人乳腺癌(MCF-7)裸鼠模型的治疗,观察其对祼鼠血管生成及肿瘤生长的抑制作用。方法将48只荷瘤鼠按随机数字表法分为A组及B组,每组24只,两组再分为化疗组、内皮抑素组、联合用药组及对照组,化疗组给予紫杉醇+顺铂(TP),紫杉醇20mg/kg,腹腔注射,第1、7、14天,顺铂5mg/kg,腹腔注射,第1、7天;内皮抑素组给予重组人内皮抑素10mg/kg,静脉推注,连续14d;联合用药组给予重组人内皮抑素+TP:紫杉醇20mg/kg,腹腔注射,第1、7、14天,顺铂5mg/kg,腹腔注射,第1、7天,重组人内皮抑素10mg/kg,静脉推注;对照组连续14d静脉推注等体积生理盐水,比较各组的抑瘤率,绘制肿瘤生长曲线。ELISA方法检测血清血管内皮生长因子(VEGF),肿瘤组织病理切片,观察微血管密度(MVD)、凋亡指数,B组动物观察其生存期。结果联合用药组VEGF、MVD与其他各组比较明显减低(P<0.05),凋亡指数与其他各组比较明显增加(P<0.05),生存时间与对照组比较明显延长(P<0.05)。结论重组人内皮抑素联合TP方案治疗人乳腺癌裸鼠移植瘤对肿瘤生长及肿瘤血管抑制优于单一化疗,但1个周期联合化疗用药不能延长生存期。Objective To investigate the anti-angiogenesis and tumor inhibitory effects of recombinant human endostatin （rhES） combined with paclitaxel-cisplatin chemotherapy （TP regimen） on xenograft tumors in nude mice of human breast carcinoma cell MCF-7. Methods Forty-eight xenograft nude mice were randomized into group A and group B ,then every group were divided 4 subgroups, that is, TP group （cisplatin 20 mg/kg at days 1, 7 and 14, and paclitaxel 5 mg/kg at days 1 and 7, i. p. ）, rhES group （rhES 10 mg·kg^-·d^-1 for 14 d, i.v. ）, rhES ＋ TP group （ combined treatment as above-mentioned）, and control group （ normal saline, i. v. ）. Inhibitory rate of xenograft determined by ELISA, microvessel and tumor growth curve was calculated and plotted. Serum VEGF level was density （MVD） in tumors was measured by immunohistochemistry, and cell apoptosis was examined by TUNEL staining. Survival time was observed in group B. Results Serum VEGF and MVD was significantly lower in rhES ＋ TP group than in other groups （P 〈 0.05 ）, but its apoptosis index was higher （P 〈 0.05 ）. Survival time had no difference in rhES ＋ TP group than in TP group, but was longer than that of control group （P 〈 0.05）. Conclusion rhES combined TP regimen is better than TP regimen in tumor growth and microvessel growth of human breast cancer xenograft, but the survival is not significant prolonged within one treatment cycle.

关 键 词：乳腺癌 重组人内皮抑素 化疗 裸鼠 

分 类 号：R73-36[医药卫生—肿瘤] R737.9[医药卫生—临床医学]