An RGD-Modified Endostatin-Derived Synthetic Peptide Shows Antitumor Activity in Vivo
It has been reported that an cndostatin-derivcd synthetic peptide, named ES-2, that contains the amino acids 60-70 of endostatin from its N terminus, efficiently inhibits basic fibroblast growth factor-induced directional migration and tubular morphogenesis of microvascular endothelial cells. We found that the peptide had no effects on tumor growth in vivo. However, when the peptide Arg-Gly-Asp (RGD) was introduced into ES-2, the modified ES-2 showed significant antitumor results in animal models. Histochemical and immunohistochemical analysis showed that RGD-modified ES-2 induced large areas of continuous necrosis within tumors and significantly reduced the vessel density compared to control. Furthermore, only the peptides with RGD were able to bind tumor cells in vitro, suggesting that additional RGD domains may help in improving the receptor-binding ability and pharmacokinctic properties of ES-2 and preventing organic clearance, as well as enzymalic degradation of the peptide, thus enabling a greater fraction of the administered dose to be biologically available.
Luosheng Chen Sami Siraj Xiaofeng Huang Min Wang Huisheng Fang Runting Yin Han-Mei Xu Ying Wang
Department of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, and Department of Oral Pathology, Nanjing Stamotology Hospital.Affiliated Medical School, Nanjing University, 210008, P.R.China
国际会议
广州
英文
577-583
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）