Herceptin联合顺铂对高表达HER-2／neu卵巢癌移植瘤鼠的治疗作用  

Therapeutic effect of herceptin combined with cDDP on mice receiving implan-tation of HER-2/neu-overexpression human ovarian cancer

作　　者：李爱华[1] 靳卫国[1] 刘薇[1] 任玉波[1] 周宏[1] 孔爱荣[1] 

机构地区：[1]聊城市人民医院妇科,山东聊城252000

出　　处：《中国肿瘤生物治疗杂志》2006年第1期50-53,共4页Chinese Journal of Cancer Biotherapy

基　　金：山东省卫生厅青年科技基金资助

摘　　要：目的:建立高表达HER-2／neu的人卵巢癌细胞株SKOV3裸鼠腹腔移植瘤模型,探讨Herceptin联合顺铂(cisplan- tin,cDDP)的治疗作用及其机制。方法:将人卵巢癌细胞株SKOV3接种于裸鼠腹腔,96 h后随机分为4组进行腹腔内注射治疗:对照A组生理盐水,B组cDDP 3 mg／kg,c组Herceptin 1 mg／kg,D组cDDP 3 mg／kg加Herceptin 1 mg/kg,观察各组裸鼠成瘤率、生存期、生存延长率;采用流式细胞术检测不同治疗后肿瘤细胞中Fas、FasL的表达情况;分别取A、D组肿瘤组织予病理学检查及免疫组化染色,观察组织学变化。结果:SKOV3裸鼠腹腔移植瘤HER-2／neu免疫组化染色为++,联合用药后HER-2／neu染色减弱,且凋亡现象明显。Herceptin与cDDP联合用药可明显延长荷瘤鼠的生存期,与单药相比有显著性差异(P<0．05)。Herceptin、cDDP及联合用药后,Fas表达率均明显升高(P<0．01),但以联合用药组表达率最高;而FasL表达率各治疗组较对照组无显著性差异。结论:Herceptin、cDDP能有效抑制高表达HER-2／neu SKOV3裸鼠腹腔移植瘤的生长, 延长荷瘤裸鼠的生存期,联合用药组疗效最为显著,其机制与CD95调节有关。Objective： To establish abdomino-metastasis model of human ovarian carcinoma cell strain SKOV3 （overexpressed HER-2/neu） in nude mice, and to explore the inhibitory effect and mechanism of herceptin combined with cDDP on mice model. Methods： Ninety-six hours after SKOV3 cell were implanted into abdominal cavity, nude mice were randomly divided into 4 groups： A group normal saline, B group cDDP, C group herceptin and D group herceptin plus cDDP. The tumor formation rate, survival time and prolongation survival time of tumor-bearing nude mice were evaluated. The changes of Fas and FasL were estimated by flow cytometry（FCM）, ttER-2/neu in tissue of group A and D was detected with pathological and immunohistochemistry method. Results： HER-2/neu was overexpressed in abdominal cavity implanted with SKOV3 tumors; herceptin combined with cDDP decreased the contents of HER-2/neu. Herceptin and cDDP significantly inhibited abdomino-plantation of SKOV3 in nude mice, and prolonged their survival time. Flow cytometry showed significant difference in apoptosis rate between control group and other groups（ P =0. 001 ）. The highest apoptosis rate was 55.9% in the combination group ; the expression of FasL was not significantly different between control group and other groups. Conclusion： Herceptin and cDDP can inhibit the growth of SKOV3 ceils and prolong the survival duration of tumor-bearing nude mice and the mechanism may be associated with the positive regulation of CD95.

关 键 词：Hereeptin 顺铂 卵巢肿瘤 HER-2/NEU 裸鼠 凋亡 

分 类 号：R730[医药卫生—肿瘤]