Open AccessNorcantharidin inhibits tumor angiogenesis via blocking VEGFR 2/ MEK / ERK signaling pathways
Author(s) -
Zhang Long,
Ji Qing,
Liu Xuan,
Chen Xingzhu,
Chen Zhaohua,
Qiu Yanyan,
Sun Jian,
Cai Jianfeng,
Zhu Huirong,
Li Qi
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12120
Subject(s) - angiogenesis , mapk/erk pathway , human umbilical vein endothelial cell , vascular endothelial growth factor , cancer research , mek inhibitor , signal transduction , microbiology and biotechnology , p38 mitogen activated protein kinases , kinase , kinase insert domain receptor , chemistry , umbilical vein , angiogenesis inhibitor , phosphorylation , endothelial stem cell , vascular endothelial growth factor a , biology , vegf receptors , biochemistry , in vitro
Norcantharidin ( NCTD ), the demethylated form of C antharidin, a reagent isolated from blister beetles, has been shown to be an anti‐tumor agent capable of inhibiting proliferation as well as inducing apoptosis in many cancer cell lines. However, little is known about the effect of NCTD in tumor angiogenesis. In this study, we demonstrated that NCTD inhibited vascular endothelial growth factor ( VEGF )‐induced cell proliferation, migration, invasion, and capillary tube formation of primary human umbilical vein endothelial cells ( HUVEC s) in a dose‐dependent manner. Furthermore, we showed NCTD inhibited tumor growth and angiogenesis of colon cancer cells ( LOVO ) in vivo . We then mechanistically described that NCTD specifically abrogated the phosphorylation/activation of vascular endothelial growth factor receptor‐2 ( VEGFR 2)/ MEK / ERK pathway kinases, with little effect on the phosphorylation of p38 MAPK and A kt, and on C ox‐2 expression. In summary, our results indicate that NCTD is a potential inhibitor of tumor angiogenesis by blocking VEGFR 2/ MEK / ERK signaling.