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

作者:Hou, Ying; Chu, Min; Cai, Yanfei; Lei, Jianyong; Chen, Yun; Zhu, Ruiyu; Gong, Xiaohai; Ma, Xin; Jin, Jian*
来源:Molecular Medicine Reports, 2015, 12(2): 2360-2366.
DOI:10.3892/mmr.2015.3636

摘要

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 mu M. 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 mu M) inhibited the proliferation, migration and tube formation of vascular endothelial EA. hy926 cells. G(0)/G(1) arrest (10.96+/-1.40%) and apoptotic cells (55.85+/-1.06%) were observed in the EA. hy926 cells treated with 4 mu M and 6 mu M 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.