A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity
Experimental & Molecular Medicine
; : 514-523, 2010.
Article
em En
| WPRIM
| ID: wpr-214628
Biblioteca responsável:
WPRO
ABSTRACT
Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF- and tumor conditioned medium-induced proliferation and ERK signaling of endothelial cells, and VEGF-induced migration and tube formation of endothelial cells. Moreover, MAP2-dRK6 blocks in vivo growth of VEGF-secreting colorectal cancer cells by the suppression of angiogenesis and the subsequent induction of tumor cell apoptosis. Our observations suggest that MAP2-dRK6 can be a prospective therapeutic molecule or lead compound for the development of drugs for various VEGF-related angiogenic diseases.
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Texto completo:
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Índice:
WPRIM
Assunto principal:
Peptídeos
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Dados de Sequência Molecular
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Neoplasias Colorretais
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Movimento Celular
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Sequência de Aminoácidos
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Neovascularização Fisiológica
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Inibidores da Angiogênese
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Células Endoteliais
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Soro
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Fator A de Crescimento do Endotélio Vascular
Limite:
Animals
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Humans
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2010
Tipo de documento:
Article