Abstract |
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 6.25-50microg/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.
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Authors | Chuannan Xiong, Haige Wu, Peng Wei, Ma Pan, Yaqin Tuo, Isao Kusakabe, Yuguang Du |
Journal | Carbohydrate research
(Carbohydr Res)
Vol. 344
Issue 15
Pg. 1975-83
(Oct 12 2009)
ISSN: 1873-426X [Electronic] Netherlands |
PMID | 19631932
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Oligosaccharides
- Tissue Inhibitor of Metalloproteinase-1
- Vascular Endothelial Growth Factor A
- Tissue Inhibitor of Metalloproteinase-2
- chitohexaose
- Chitosan
- Urokinase-Type Plasminogen Activator
- Matrix Metalloproteinase 9
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Topics |
- Cell Line
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Chitosan
(chemistry)
- Chromatography, High Pressure Liquid
- Gene Expression
(drug effects)
- Humans
- Matrix Metalloproteinase 9
(genetics)
- Molecular Structure
- Neovascularization, Physiologic
(drug effects)
- Oligosaccharides
(chemistry, pharmacology)
- Reverse Transcriptase Polymerase Chain Reaction
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Tissue Inhibitor of Metalloproteinase-1
(genetics)
- Tissue Inhibitor of Metalloproteinase-2
(genetics)
- Urokinase-Type Plasminogen Activator
(genetics)
- Vascular Endothelial Growth Factor A
(genetics)
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