A Study On The Anti-breast Cancer Activity Of Heparan Sulfate Analogs

Basic Fibroblast Growth Factor(bFGF), with its particular functions in promoting proliferation of cancer cells and angiogenesis, plays a pretty significant role in the breast cancer cells' growth, differentiation, migration and. With heparin sulfate, bFGF binds to FGFR, leading to the dimerization of FGFR, and consequently activates multiple signaling transduction pathways in cells, such as Ras-MAPK cascade, JAK/STAT and so on.Heparan binds bFGF by electrostatic interactions and hydrogen bond, thus lead to the binding of bFGF and FGFR as well as the intracellular signal transduction. There are basic amino acid residues in the binding domain and aromatic amino acid residues besides the binding domain. Polysaccharides may inhibit the binding of bFGF and HS by binding with the residues. Therefore modified heparan sulfate similarity is now the hot spot of research on anti-breast cancer drugs.By [3H]-Thymidine incorporation, Immunoblotting and Flow cytometry, we test the anti-breast cancer activities of heparan sulfate similarity on MCF-7 wild type cell line and MCF-7ras that derived from MCF-7. We found that heparan sulfate similarity can inhibit the proliferation of MCF-7, this may be caused by the inhibition of Ras-ERK signal pathway stimulation mediated by bFGF and apoptosis induction. Over-expressed Ras can inhibit such effect of heparan sulfate similarity, the reason may be that over-expressed Ras maintains the intracellular ERK activation in a high level so that it needs not extracellular bFGF mediation and the highly activated ERK may resist apoptosis.