Effects of an Engineered Anti-HER2 Antibody chA21 on Invasion of Human Ovarian Carcinoma Cell In Vitro  

作　　者：Yi Gao Qiang Wu Zheng-sheng Wu Gui-hong Zhang An-li Zhang 

机构地区：[1]Department of Pathology, Anhui Medical University, Hefei 230032, China

出　　处：《Chinese Journal of Cancer Research》2011年第2期147-152,共6页中国癌症研究（英文版）

基　　金：supported by National "863" High-Tech R & D Program of China (No. 2004AA215260);Science Foundation for Young Teacher of Anhui Province (No.2008jq1062);Research Foundation for Advanced Talents of the No.2 Hospital affiliated to the Anhui Medical University (No. 2009-08)

摘　　要：Objective： HER-2 plays an important role in the development and progression of ovarian carcinoma. A number of monoclonal antibodies （MAbs） and engineered antibody fragments （such as scFvs） against the subdomain II or IV of HER-2 extracellular domain （ECD） have been developed. We investigated the effect of chA21, an engineered anti-HER-2 antibody that bind primarily to subdomain I, on ovarian carcinoma cell invasion in vitro, and explored its possible mechanisms. Methods： Growth inhibition of SK-OV-3 cells was assessed using a Methyl thiazolyl tetrazolium （MTT） assay. The invasion ability of SK-OV-3 was determined by a Transwell invasion assay. The expression of matrix metalloproteinase-2 （MMP-2） and its tissue inhibitors （TIMP-2） was detected by immunocytochemical staining, and the expression of p38 and the phosphorylation of p38 were assayed by both immunocytochemistry and Western blot. Results： After treatment with chA21, the invasion of human ovarian cancer SK-OV-3 cells was inhibited in dose- and time-dependent manners. Simultaneously the expression of p38, phospho-p38, MMP-2 and the MMP-2/TIMP-2 ratio decreased, while TIMP-2 expression increased. Additionally, the decrease in phospho-p38 was much greater than that of p38. Conclusion： chA21 may inhibit SK-OV-3 cell invasion via the signal transduction pathway involving MMP-2, TIMP-2, p38 and the activation of p38MAPK.Objective： HER-2 plays an important role in the development and progression of ovarian carcinoma. A number of monoclonal antibodies （MAbs） and engineered antibody fragments （such as scFvs） against the subdomain II or IV of HER-2 extracellular domain （ECD） have been developed. We investigated the effect of chA21, an engineered anti-HER-2 antibody that bind primarily to subdomain I, on ovarian carcinoma cell invasion in vitro, and explored its possible mechanisms. Methods： Growth inhibition of SK-OV-3 cells was assessed using a Methyl thiazolyl tetrazolium （MTT） assay. The invasion ability of SK-OV-3 was determined by a Transwell invasion assay. The expression of matrix metalloproteinase-2 （MMP-2） and its tissue inhibitors （TIMP-2） was detected by immunocytochemical staining, and the expression of p38 and the phosphorylation of p38 were assayed by both immunocytochemistry and Western blot. Results： After treatment with chA21, the invasion of human ovarian cancer SK-OV-3 cells was inhibited in dose- and time-dependent manners. Simultaneously the expression of p38, phospho-p38, MMP-2 and the MMP-2/TIMP-2 ratio decreased, while TIMP-2 expression increased. Additionally, the decrease in phospho-p38 was much greater than that of p38. Conclusion： chA21 may inhibit SK-OV-3 cell invasion via the signal transduction pathway involving MMP-2, TIMP-2, p38 and the activation of p38MAPK.

关 键 词：HER-2 Ovarian neoplasms INVASION p38 mitogen-activated protein kinase Matrix metalloproteinase-2 Tissue inhibitor of matrix metalloproteinase-2 

分 类 号：Q279[生物学—细胞生物学] S852.43[农业科学—基础兽医学]