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Antitumor and antiangiogenic activity of the recombinant human disintegrin domain of A disintegrin and metalloproteinase 15

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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 ArgGlyAsp motif in its disintegrin domain. In the present study, the antitumor and antiangiogenic 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 1.06.0 µM. In addition, rhddADAM15 inhibited the proliferation of Bel7402 cells via the mitogenactivated protein kinase pathway and reduced the activation of Src. rhddADAM15 (110 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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Document Type: Research Article

Affiliations: 1: Laboratory of Molecular Pharmacology and Drug Design, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China 2: Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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