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Chin J Cancer Res. 2011 Jun;23(2):147-52. doi: 10.1007/s11670-011-0147-7.

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

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1
Department of Pathology, Anhui Medical University, Hefei 230032, China.

Abstract

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.

KEYWORDS:

HER-2; Invasion; Matrix metalloproteinase-2; Ovarian neoplasms; Tissue inhibitor of matrix metalloproteinase-2; p38 mitogen-activated protein kinase

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