抗HER2工程抗体chA21和Herceptin对人卵巢癌SKOV3裸小鼠移植瘤的抑制作用
移植瘤,,工程抗体;HER2;chA21;Herceptin;SKOV3;移植瘤;Ki67;NFκB,抗HER2工程抗体chA21和Herceptin对人卵巢癌SKOV3裸小鼠移植瘤的抑制
摘要:目的:研究抗HER2工程抗体Herceptin及chA21对高表达HER2的人卵巢癌SKOV3裸小鼠移植瘤的生长抑制作用及其机制。方法:建立人卵巢癌SKOV3裸小鼠移植瘤模型,随机分组,Herceptin和chA21均按30mg/kg体重每周两次静脉注射,连续6周给药,观察肿瘤生长变化,计算抑瘤率;利用组织芯片及免疫组化方法结合显微图像分析系统定量检测肿瘤细胞Ki67和NFκB的表达。结果:Herceptin(30mg/kg)和chA21(30mg/kg)能显著抑制SKOV3移植瘤的生长,抑瘤率分别为51.12%和30.53%。Herceptin组和chA21组肿瘤组织Ki67和NFκB的表达显著低于对照组(P<0.01),而两组之间比较统计学无显著性差异(P>0.05)。结论:chA21和Herceptin均能抑制高表达HER2的SKOV3移植瘤的生长。通过抑制NFκB的表达而影响肿瘤细胞的增殖是其可能的共同分子机制之一。关键词:工程抗体;HER2;chA21;Herceptin;SKOV3;移植瘤;Ki67;NFκB
Antitumor effect of antiHER2 engineering antibodies Herceptin and
chA21 on nude mice xenografts of human ovarian cancer SKOV3 cellsLing Xiaoguang, Wu Qiang, Xue Hua, Yang Feng, Cheng Liansheng, Liu Jing
(1. Department of Pathology, Anhui Medical University, Hefei 230032;
2. School of Life Science, University of Science and Technology of China, Hefei 230027, China)
ABSTRACT: Objective To study the antitumor effect of antiHER2 engineering antibodies chA21 and Herceptin on nude mice xenografts of human ovarian cancer SKOV3 cells and explore its mechanism. Methods An animal model with human ovarian cancer SKOV3 cells involved in nude mice was established and the mice were randomized into 3 groups: normal saline(NS), chA21 and Herceptin. The mice were respectively administrated with Herceptin (30mg/kg) and chA21 (30mg/kg) via caudal vein injection twice a week for consecutive 6 weeks, and then were killed after 44 days adminstration of the drugs. The volumes of the xenografts were measured twice a week. The tumor weight and inhibition ratio were measured after mice were killed. Ki67 and NFκB expression in the three groups was quantificationally analyzed by immunohistochemistry on tissue microarray sections combined with a microimage analysing system. Results The growth of xenografts of human ovarian cancer SKOV3 cells in nude mice was significantly inhibited by either Herceptin or chA21. Both Ki67 labeling indices and NFκB levels in chA21 and Herceptin groups were lower than those in the control(P<0.01). Conclusion Herceptin and chA21 may inhibit the growth of transplantations of human ovarian cancer SKOV3 cells.Down regulation of NFκB expression in SKOV3 cells might be one of their possible mechanisms. ......
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