BioScience Trends
Online ISSN : 1881-7823
Print ISSN : 1881-7815
ISSN-L : 1881-7815
Original Articles
A novel semi-synthetic andrographolide analogue A5 inhibits tumor angiogenesis via blocking the VEGFR2-p38/ERK1/2 signal pathway
Chenyuan GongChong XuLili JiZhengtao Wang
Author information
JOURNALS FREE ACCESS

2013 Volume 7 Issue 5 Pages 230-236

Details
Abstract

The present study is designed to observe the inhibitory effect of compound A5, a semi- synthetic analogue of the natural compound andrographolide, on angiogenesis and its underlying mechanism. Compound A5 is semi-synthesized from natural compound neoandrographolide. Andrographolide, the aglycon of neoandrograoholide, and A5 all inhibited vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs) proliferation, and that the inhibition shown by A5 is the best. A5 also inhibited VEGF-induced tube formation in HUVECs in a concentration-dependent manner. VEGF-induced neoangiogenesis in vivo was observed by Matrigel formation assay. The Matrigel picture and CD31 staining results showed that A5 inhibited VEGF-induced neoangiogenesis in vivo. Further, Western-blot results showed that A5 inhibited VEGF- induced phosphorylation of VEGF receptor 2 (VEGFR2), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38 kinase. The antitumor effect of A5 was analyzed in a xenograft mouse tumor model inoculated with hepatoma Hep3B cells. The results showed that A5 decreased tumor weight and tumor size without affecting body weight in the xenograft mouse, and A5 also decreased CD31 staining in tumor tissue. Taken together, the present study demonstrates that compound A5 inhibits tumor growth via blocking neoangiogenesis, and the cellular VEGFR2-p38/ERK1/2 signal pathway.

Information related to the author
© 2013 International Research and Cooperation Association for Bio & Socio-Sciences Advancement
Previous article Next article
feedback
Top