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KMID : 0620920100420070514
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Experimental & Molecular Medicine
2010 Volume.42 No. 7 p.514 ~ p.523
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A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity
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Kim Jung-Wook
Kim Tae-Dong
Hong Bok-Sil
Kim Oh-Youn
Yoon Wan-Hee
Chae Chi-Bom
Gho Yong-Song
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Abstract
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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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KEYWORD
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angiogenesis inhibitors, colorectal neoplasms, peptides, receptors, vascular endothelial growth factor, vascular endothelial growth factors
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