INHIBITION OF ANGIOGENESIS BY ERBSTATIN, AN INHIBITOR OF TYROSINE KINASE

Abstract

Here we describe the inhibitory effect of erbstatin, a specific tyrosine kinase inhibitor, on in vivo angiogenesis. Inhibition of angiogenesis was determined in a bioassay system involving chorioallantoic membranes of growing chick embryos. Erbstatin produced a dose-dependent inhibitory action on embryonic angiogenesis. This inhibition occurred at as small a dose as 10 ng/egg and the ID₅₀ value was 80 ng/egg. To analyze this inhibition, in vitro experiments involving vascular endothelial cells were also performed. Erbstatin affected the proliferation of vascular endothelial cells, one of angiogenic components. This inhibition was dose-dependent, the IC₅₀ value being 3.6 μM. These data indicate that erbstatin-sensitive tyrosine kinase(s) is involved in angiogenic endothelial cell proliferation, and that experiments involving erbstatin will provide an important clue to understand a mechanism of angiogenesis.