SPF110 inhibited the angiogenesis in zebrafish embryos and repressed the VEGF mediated effects in endothelial cells ABSTRACT A protein factor with a molecular weight of 110 kDa from shark cartilage was extracted, and its antiangiogenesis activity was determined using zebrafish model. Our results indicated that the vessel growth was significantly repressed when the SPF110 was included in the media with an IC50 of 0.25 μg/μL, as analyzed by vessel staining methods. To clarify if the antiangiogenesis of SPF110 was correlated with VEGF, human VEGF was microinjected into zebrafish embryos at the 1-4 cell stage. Significantly increase of the vessel growth was found in VEGF microinjected embryos. However, when 0.25/ul SPF was added in the media, the VEGF mediated effect of vessel growth was decreased. To confirm if the antiangiogenesis effects of SPF110 in zebrafish embryos were related with human endothelial cells, receptor binding and tyrosine phosporylation experiments were also performed. Our results confirmed that SPF110 could strongly compete against the binding of VEGF to its receptor in endothelial cells and significantly inhibited the VEGF-dependent tyrosine phosphorylation of VEGF receptor-2, whereas it had no significant effect on VEGF receptor-1 activity. Our results suggested that the SPF110 could be developed as a novel anticancer agent, and also the zebrafish is an ideal antiangiogenesis model for assessing the drug effects and screening anticancer drugs.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]