Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells

Biochem Biophys Res Commun. 2013 Jun 14;435(4):640-5. doi: 10.1016/j.bbrc.2013.05.037. Epub 2013 May 18.

Abstract

ADAM15 (A Disintegrin And Metalloproteinase 15), a transmembrane protein containing seven domains, interacts with some integrins via its disintegrin domain and overexpresses in many solid tumors. In this study, the effect of the recombinant human disintegrin domain (rhddADAM15) on the proliferation and migration of Bel-7402 cells was evaluated in vitro and in vivo in zebrafish xenografts. rhddADAM15 (4 μM) severely inhibited the proliferation and migration of Bel-7402 cells, inducing a partial G2/S arrest and morphological nucleus changes of apoptosis. Moreover, the activity of caspases 8, 9 and 3 in Bel-7402 cells was increased. In addition, the zebrafish was used as a model for apoptosis-induction and tumor-xenograft. rhddADAM15 (1 pM) inhibited the growth and metastasis of Bel-7402 cell xenografts in zebrafish and a lower concentration (0.1 pM) induced severe apoptosis in the somatic cells of zebrafish. In conclusion, our data identified rhddADAM15 as a potent inhibitor of tumor growth and metastasis, making it a promising tool for use in anticancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disintegrins / genetics
  • Disintegrins / pharmacology*
  • Humans
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / physiopathology*
  • Membrane Proteins / genetics
  • Membrane Proteins / pharmacology*
  • Protein Structure, Tertiary
  • Recombinant Proteins / pharmacology

Substances

  • Disintegrins
  • Membrane Proteins
  • Recombinant Proteins
  • ADAM Proteins
  • ADAM15 protein, human