SUPPRESSION MECHANISM OF ANGIOGENESIS BY PSK

抄録

PSK (Krestin), a protein-bound polysaccharide, is known to be an immunomodulating agent. In addition, PSK was reported to have an anti-angiogenic effect in vivo, but the mechanism was unknown. In this study, we investigated the mechanism by which PSK affects angiogenesis. PSK inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) in the absence of basic fibroblast growth factor (bFGF) but inhibited more effectively in its presence. PSK at a high concentration slightly suppressed tube formation of HUVECs and their adhesion to extracellular matrix proteins. PSK also suppressed the bFGF-dependent MAP kinase phosphorylation. A gel filtration experiment demonstrated direct binding of PSK to ¹²⁵I-bFGF. PSK (5mg/kg, i. v.) injection reduced the bFGF-induced angiogenesis in an in vivo rat cornea assay. These data suggest that PSK binds to bFGF and interferes with its signal transduction to inhibit the proliferation of HUVECs, resulting in the suppression of angiogenesis.