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Open Access 01-12-2010 | Research

Augmented inhibition of angiogenesis by combination of HER2 antibody chA21 and trastuzumab in human ovarian carcinoma xenograft

Authors: Anli Zhang, Guodong Shen, Ting Zhao, Guihong Zhang, Jing Liu, Lihua Song, Wei Wei, Ling Bing, Zhengsheng Wu, Qiang Wu

Published in: Journal of Ovarian Research | Issue 1/2010

Abstract

Background

chA21 is a novel tumor-inhibitory antibody which recognized subdomain I of HER2 extracellular domain with an epitope distinct from other HER2 antibodies. Previously, we demonstrated that chA21 inhibits human ovarian carcinoma cell line SKOV-3 growth in vitro and in vivo study. In this study, we further investigated the anti-angiogenic efficacy combination of chA21 with trastuzumab in SKOV-3 xenograft model.

Methods

Nude mice were s.c. challenged with SKOV-3 cells and received treatment of chA21 alone, trastuzumab alone or both antibodies together twice a week for 21 days. Tumor volume and microvessel density (MVD) were evaluated. The effect of chA21 plus trastuzumab treament on vascular endothelial growth factor (VEGF) secretion, endothelial cells proliferation and migration, and the status of HER2 downstream pathway AKT/phosphorylated AKT (pAKT) were evaluated in vitro.

Results

In vivo study combination of chA21 with trastuzumab resulted in reduce tumor growth and angiogenesis than each monotherapy. In vitro study, the combination of chA21 with trastuzumab inhibits VEGF secretion, endothelial cells proliferation and migration. Furthermore, the combination treatment inhibits pAKT expression.

Conclusion

Our findings suggested that the combination of chA21 with trastuzumab can cause augmented inhibition of angiogenesis in SKOV-3 xenograft model. Inhibition of agniogenesis may through suppression of AKT pathway. The therapeutic benefits of combination chA21 with trastuzumab warrant further study in an attempt to make the translation into the clinic.

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Title: Augmented inhibition of angiogenesis by combination of HER2 antibody chA21 and trastuzumab in human ovarian carcinoma xenograft
Authors: Anli Zhang
Guodong Shen
Ting Zhao
Guihong Zhang
Jing Liu
Lihua Song
Wei Wei
Ling Bing
Zhengsheng Wu
Qiang Wu
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2010
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-3-20

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Augmented inhibition of angiogenesis by combination of HER2 antibody chA21 and trastuzumab in human ovarian carcinoma xenograft

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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