抗HER-2嵌合抗体chA21对卵巢癌细胞MMP-2和TIMP-2表达的影响  

Effect of anti-HER-2 engineered antibody chA21 on MMP-2 and TIMP-2 expression of human ovarian cancer SKOV3 cells

作　　者：高毅[1] 吴强[1] 凌晓光[1] 程联胜[2] 刘兢[2] 

机构地区：[1]安徽医科大学病理学教研室,安徽合肥230032 [2]中国科学技术大学生命科学院,安徽合肥230027

出　　处：《西安交通大学学报（医学版）》2007年第4期368-371,383,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家"863"计划资助项目(No.2001AA215381);安徽省自然科学研究基金资助项目(No.03043701)

摘　　要：目的观察抗HER-2嵌合抗体chA21对卵巢癌细胞MMP-2和TIMP-2表达的影响。方法采用免疫细胞化学法检测不同质量浓度chA21(6 mg/L和12mg/L组)作用36 h后,培养的高表达HER-2人卵巢癌细胞株SKOV3中MMP-2和TIMP-2表达的变化;建立SKOV3裸小鼠移植瘤模型,制作组织芯片,观察chA21(30 mg/kg)对肿瘤组织MMP-2和TIMP-2表达的作用。结果细胞实验显示,随着chA21浓度的升高,MMP-2明显降低(P<0.01,r=-0.945),而TIMP-2显著升高(P<0.01,r=0.926),MMP-2/TIMP-2比值也明显降低(P<0.01,r=-0.945),且均呈浓度依赖性改变;裸鼠荷瘤实验结果显示,chA21能明显下调MMP-2的表达(P<0.01),上调TIMP-2的表达(P<0.01),并使MMP-2/TIMP-2明显降低(P<0.01)。结论chA21能调节高表达HER-2人卵巢癌细胞SKOV3的MMP-2和TIMP-2表达水平。To investigate the effect of an anti-HER-2 engineered antibody, chA21, on the expression of MMP-2 and TIMP-2 in human ovarian cancer SKOV3 cells that highly express HER-2. Methods After exposure to chA21 at concentrations of 6 mg/L and 12 mg/L for 36 hours, respectively, the expression of MMP-2 and TIMP-2 proteins was detected by immunocyctochemistry. SKOV3 cells were inoculated into nude mice to establish animal models. The mice were respectively administered with normal saline and chA21 （30 mg/kg） via injection twice a week for 6 consecutive weeks, and then were killed after 44 days＇ administration of the drugs. Immnohistochemical staining of MMP-2 and TIMP-2 was observed on tissue microarray sections. Results After exposed to chA21, TIMP-2 protein was increased （P〈0.01, r = 0. 926）, while MMP-2 was decreased （P〈0.01, r = -0. 945） and MMP-2/TIMP-2 ratio was obviously lowered（P〈0.01, r =- 0. 945）. In the xenografts, TIMP-2 protein （P〈0.01） was up-regulated, while the expression of MMP-2 （P〈0.01） and the ratio of MMP-2/TIMP-2 （P〈0.01） were significantly down-regulated compared to those in control. Conclusion The balance between the expression of MMP-2 and TIMP-2 in ovarian cancer cells is regulated by anti-HER-2 engineered antibody chA21.

关 键 词：卵巢癌 嵌合抗体 CHA21 HER-2 MMP-2 TIMP-2 

分 类 号：R737.31[医药卫生—肿瘤] R394.8[医药卫生—临床医学]