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A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity
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: 1 Índice: WPRIM Assunto principal: Peptídeos / Dados de Sequência Molecular / Neoplasias Colorretais / Movimento Celular / Sequência de Aminoácidos / Neovascularização Fisiológica / Inibidores da Angiogênese / Células Endoteliais / Soro / Fator A de Crescimento do Endotélio Vascular Limite: Animals / Humans Idioma: En Revista: Experimental & Molecular Medicine Ano de publicação: 2010 Tipo de documento: Article
Texto completo: 1 Índice: WPRIM Assunto principal: Peptídeos / Dados de Sequência Molecular / Neoplasias Colorretais / Movimento Celular / Sequência de Aminoácidos / Neovascularização Fisiológica / Inibidores da Angiogênese / Células Endoteliais / Soro / Fator A de Crescimento do Endotélio Vascular Limite: Animals / Humans Idioma: En Revista: Experimental & Molecular Medicine Ano de publicação: 2010 Tipo de documento: Article