Kallikrein-binding protein suppresses growth of hepatocellular carcinoma by anti-angiogenic activity.

Effect of kallikrein-binding protein (KBP), an endogenous angiogenic inhibitor, on the growth of hepatocellular carcinoma and the possible mechanism were investigated. KBP inhibited proliferation and induced apoptosis of endothelial cells, but had no effect on the proliferation and apoptosis of hepatocarcinoma cell line HepG2. Intraperitoneal injection of KBP significantly suppressed the tumor growth and inhibited intratumoral neovascularization both in grafted hepatocarcinoma mice and xenografted hepatocarcinoma athymic mice. Moreover, KBP reduced expression of VEGF and HIF-1alpha nuclear translocation in HepG2 cells and xenografts. Down-regulation of VEGF in tumor cells through inhibiting HIF-1alpha may represent a novel mechanism for the anti-angiogenic and anti-tumor activity of KBP.