title: Enhanced anti-angiogenesis and anti-tumor activity of endostatin by chemical modification with polyethylene glycol and low molecular weight heparin.
abstract: Endostatin (ES), a potent endogenous angiogenesis inhibitor found in 1997 by O'Reilly, can effectively inhibit angiogenesis, inhibit the growth and metastasis of tumors. ES can also decrease drug resistance in long term and repeated treatment when it is used in combination with other chemotherapeutic agents. But there are still lots of obstacles on its clinical application, such as the need of a high dose to maintain its efficacy short half-life, poor stability, expensive, and some other shortcomings just like other protein drugs. Chemical modification on ES by polyethylene glycol (PEG) and low molecular weight heparin (LMWH) were successfully carried out in order to obtain a better ES derivative. Several classic experimental models were employed to study the bioactivity of ES and modified ES, including chicken chorioallantoic membrane (CAM) assay, corneal neovascularization (CNV) assay and Sarcoma 180 tumor bearing mice assay. The results showed that PEG-ES and LMWH-ES had better anti-angiogenesis and anti-tumor activity than ES, which indicates that LMWH was also a good protein modifier.
authors.affiliation: Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Science, Shandong University, Jinan, China.
authors.forename: Haining
authors.initials: H
authors.lastname: Tan
authors.forename: Shenglin
authors.initials: S
authors.lastname: Yang
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.forename: Jichao
authors.initials: J
authors.lastname: Cao
authors.forename: Guoying
authors.initials: G
authors.lastname: Mu
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003315:Cornea / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D043169:Endostatins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D012510:Sarcoma 180 / Q000098:blood supply / Q000188:drug therapy
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004337:Drug Carriers; D043169:Endostatins; D006495:Heparin, Low-Molecular-Weight; D011092:Polyethylene Glycols