[关键词]
[摘要]
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(cisplantin,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,96h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cDDP3mg/kg,C组Herceptin 1mg/kg,D组cDDP3mg/kg加Herceptin 1mg/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。
[Key word]
[Abstract]
To establish abdomino-metastasis model of human ovarian carcinoma cell strain SKOV3 (over-expressed HER-2/neu) in nude mice, and to explore the inhibitory effect and mechanism of herceptin combined with cD-D? 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 cD-DP. 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). HER-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 cells and prolong the survival duration of tumor-bearing nude mice and the mechanism may be associated with the positive regulation of CD95.
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[基金项目]
山东省卫生厅青年科技基金资助