Study On Anti-Metastasis Of Heparin Derivatives As Ligand Antagonist Of P-Selectin

Heparin belongs to the family of glycosaminoglycans (GAGs). The structure of heparin is heterogeneous and highly dispersed sulfated polysaccharides. The major repeating disaccharide unit in heparin is α-L-IdoA-2-SO₄-β(1→4)-α-D-GlcNSO₃-6-SO₄, which is called trisulfated disaccharide unit. In spite of the widespread use of heparin as an antithrombotic and anticogualant drug, it is increasingly thought to have a role in regulating a wide variety of biological prosesses, including the inflammatory response and tumor cell metastasis. P-selectin, a member of the selectin family of cell adhesion molecules, may play a important role in tumor metastases. Heparin or heparan sulfate (HS) has been proved have a potent anti-metastasis property results primarily from blockade of P-selectin.Carboxyl and sulfate groups (including the content and position )in the structure of heparin are closely related to its anticogualant activity. Both desulfated heparin and carboxyl-reduced heparin have low anticogualant activity. To determine the relationship between the structure and anti-metastasis activity, carboxyl-reduced heparin(CRH), N-desulfated heparin(NDeSH), N- and O-desulfated heparin (N/ODeSH), N-desulfated reacetylated heparin(NDeSAcH), N-andO-desulfated N-reacetylated heparin(N/ODeSAcH), 2-O-desulfated heparin(2DeSH) and 6-O-desulfated heparin (6DeSH) were prepared. To learn the influence of heparin and its derivatives on the growth of tumors, the effects on the proliferation of ACC-M tumor cells and ECV-304 endothelia cells were studies by...