title: An RGD-modified endostatin-derived synthetic peptide shows antitumor activity in vivo.
abstract: It has been reported that an endostatin-derived 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 pharmacokinetic properties of ES-2 and preventing organic clearance, as well as enzymatic degradation of the peptide, thus enabling a greater fraction of the administered dose to be biologically available.
authors.affiliation: Department of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, P. R. China. xuhanmei@yahoo.com.cn
authors.forename: Han-Mei
authors.initials: HM
authors.lastname: Xu
authors.forename: Runting
authors.initials: R
authors.lastname: Yin
authors.forename: Luosheng
authors.initials: L
authors.lastname: Chen
authors.forename: Sami
authors.initials: S
authors.lastname: Siraj
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Huisheng
authors.initials: H
authors.lastname: Fang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D043169:Endostatins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D043169:Endostatins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid