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.
Lu
Lei
L
Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510089, China.
Yang
Zhonghan
Z
Zhu
Baohe
B
Fang
Shuhuan
S
Yang
Xia
X
Cai
Weibin
W
Li
Chaoyang
C
Ma
Jian-xing
JX
Gao
Guoquan
G
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D015843:Serpins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; C051324:kallistatin