These authors contributed equally to this work.
Norcantharidin inhibits tumor angiogenesis via blocking VEGFR2/MEK/ERK signaling pathways
Version of Record online: 20 MAR 2013
© 2013 Japanese Cancer Association
Volume 104, Issue 5, pages 604–610, May 2013
How to Cite
(Cancer Sci 2013; 104: 604–610)
- Issue online: 15 APR 2013
- Version of Record online: 20 MAR 2013
- Accepted manuscript online: 31 JAN 2013 01:40AM EST
- Manuscript Accepted: 25 JAN 2013
- Manuscript Revised: 20 JAN 2013
- Manuscript Received: 10 AUG 2012
- Putuo Hospital Shanghai University of Traditional Chinese Medicine. Grant Number: 2011Y008
Norcantharidin (NCTD), the demethylated form of Cantharidin, 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 (HUVECs) 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 (VEGFR2)/MEK/ERK pathway kinases, with little effect on the phosphorylation of p38 MAPK and Akt, and on Cox-2 expression. In summary, our results indicate that NCTD is a potential inhibitor of tumor angiogenesis by blocking VEGFR2/MEK/ERK signaling.