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Biochem Biophys Res Commun ; 435(4): 640-5, 2013 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-23688428

RESUMO

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.


Assuntos
Proteínas ADAM/farmacologia , Desintegrinas/farmacologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Proteínas de Membrana/farmacologia , Proteínas ADAM/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desintegrinas/genética , Humanos , Proteínas de Membrana/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes/farmacologia
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