Journal
CARBOHYDRATE RESEARCH
Volume 344, Issue 15, Pages 1975-1983Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carres.2009.06.036
Keywords
Deacetylated chitohexaose; Angiogenesis; ECV304; Vascular endothelial growth factor; Urokinase plasminogen activator
Funding
- National High Technology Research and Development Program of China [2006AA100313, 2007AA10Z343]
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This study was performed to demonstrate the effects of deacetylated chitohexaose (hexamer) separated from a chitooligosaccharide (COS) mixture on tumor angiogenesis and its mechanism of action. Five fractions from dimer to hexamer were separated by a linear gradient solution of HCl on a cation-exchange resin. Then HCl was removed from the fractions by a charcoal column. The purity of the five fractions was analyzed by HPLC and the molecular masses were analyzed by MALDI-TOFMS. The hexamer expressed an inhibitory influence on CAM angiogenesis in a dose-dependent manner at concentrations of 6.25-50 mu g/egg. On further investigation, we found that the hexamer had no toxic effect on normal ECV304 cells, but could inhibit the proliferation and migration of tumor-induced ECV304 cells in a dose-dependent manner. The mechanism was demonstrated through the detection of mRNA expression of VEGF, MMP-9, TIMP-1, TIMP-2 and uPA by RT-PCR, which showed that the hexamer down-regulated the VEGF and uPA mRNA expressions in ECV304 cells, but up-regulated the TIMP-1 mRNA expression. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.
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