Ligustrazine inhibits B16F10 melanoma metastasis and suppresses angiogenesis induced by Vascular Endothelial Growth Factor.
Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and tube formation in a dose-dependent manner in vitro, and had limited cytotoxicity to HUVECs and normal fibroblasts even at a dose up to 100 microg/ml. Ligustrazine also suppressed VEGF-induced rat aortic ring sprouting dose-dependently. Invivo, Ligustrazine reduced the Hb content in a Matrigel plug implanted in mice and inhibited new vessel formation in CAM. In addition, in a B16F10 spontaneous metastasis model, Ligustrazine decreased the expression of CD34 and VEGF in primary tumor tissue and reduced the number of metastasis nodi on the lung surface. Our data suggests that Ligustrazine may inhibit tumor metastasis, at least in part, through its anti-angiogenic activity.
Chen
Lei
L
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China.
Lu
Yin
Y
Wu
Jia-ming
JM
Xu
Bo
B
Zhang
Li-juan
LJ
Gao
Ming
M
Zheng
Shi-zhong
SZ
Wang
Ai-yun
AY
Zhang
Chang-bin
CB
Zhang
Wei-wei
WW
Lei
Na
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D011719:Pyrazines; D042461:Vascular Endothelial Growth Factor A; C017953:tetramethylpyrazine