Antitumor and anti‑angiogenic activity of the recombinant human disintegrin domain of A disintegrin and metalloproteinase 15

Hou,Ying; Chu,Min; Cai,Yanfei; Lei,Jianyong; Chen,Yun; Zhu,Ruiyu; Gong,Xiaohai; Ma,Xin; Jin,Jian

doi:10.3892/mmr.2015.3636

August-2015 Volume 12 Issue 2

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August-2015 Volume 12 Issue 2

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Article

Antitumor and anti‑angiogenic activity of the recombinant human disintegrin domain of A disintegrin and metalloproteinase 15

Authors:
- Ying Hou
- Min Chu
- Yanfei Cai
- Jianyong Lei
- Yun Chen
- Ruiyu Zhu
- Xiaohai Gong
- Xin Ma
- Jian Jin
View Affiliations / Copyright

Affiliations: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China
Pages: 2360-2366
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Published online on: April 16, 2015

https://doi.org/10.3892/mmr.2015.3636
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Abstract

A disintegrin and metalloproteinases (ADAMs), a family of transmembrane glycoproteins, are expressed in numerous tissues and organs, and have been implicated in a variety of physiological and pathological processes. ADAM15 is unique among the ADAMs in having an Arg‑Gly‑Asp motif in its disintegrin domain. In the present study, the antitumor and anti‑angiogenic effects of the recombinant human disintegrin domain (rhdd) ADAM15, expressed by Escherichia coli, were evaluated. rhddADAM15 inhibited the proliferation and migration of several tumor cells, with a half maximal inhibitory concentration of 1.0‑6.0 µM. In addition, rhddADAM15 inhibited the proliferation of Bel‑7402 cells via the mitogen‑activated protein kinase pathway and reduced the activation of Src. rhddADAM15 (1‑10 µM) inhibited the proliferation, migration and tube formation of vascular endothelial EA.hy926 cells. G0/G1 arrest (10.96±1.40%) and apoptotic cells (55.85±1.06%) were observed in the EA.hy926 cells treated with 4 µM and 6 µM rhddADAM15, respectively. In vivo, rhddADAM15 significantly inhibited angiogenesis in zebrafish. rhddADAM15 at concentrations of 20 nmol/fish or 5 nmol/fish inhibited the angiogenesis of subintestinal and intersegmental vessels in the zebrafish by 72±1.26 and 48±2.92%, respectively. In conclusion, the results of the present study identified rhddADAM15 as a potent inhibitor of tumor formation and angiogenesis, rendering it a promising tool for use in anticancer treatment.

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