Effect of Vascular Endothelial Growth Factor and Its Receptor Inhibitor on Proliferation and Invasion in Bladder Cancer

2009 ◽  
Vol 83 (1) ◽  
pp. 98-106 ◽  
Author(s):  
Ryoichi Nakanishi ◽  
Natsuo Oka ◽  
Hiroyoshi Nakatsuji ◽  
Takahiro Koizumi ◽  
Manabu Sakaki ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Bladder Cancer ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Proliferation And Invasion ◽  
Receptor Inhibitor

scholarly journals Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cai Hai-rong ◽  
Huang Xiang ◽  
Zhang Xiao-rong
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Bladder Cancer ◽  
Growth Factor ◽  
Natural Product ◽  
Tumor Angiogenesis ◽  
Bladder Tumor ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Human Bladder ◽  
Endothelial Growth Factor

Abstract Angiogenesis is a vital step during the process of oncogenesis of a lot of tumors, with no exception in bladder cancer. One of the useful strategies for the development of new drugs against cancer is targeting angiogenesis. In the present study, we found that a small-molecule natural product, which belonged to the β-carboline alkaloid, named harmine, could strongly inhibit tumor angiogenesis thus exhibiting its ideal treatment efficacy in bladder cancer. In vivo study verified that harmine had the effect of inhibition on human bladder tumor xenograft growth. The inhibitory effect of harmine to bladder cancer growth was coordinated by the effects shown on angiogenesis. To further explore the pharmacological activities of harmine, we tested harmine’s influence on blood vessel formation and found that harmine effectively blocked the microvessel sprouting in rat aortic ring assay when stimulated by vascular endothelial growth factor (VEGF). Furthermore, harmine inhibited human umbilical vein endothelial cell (HUVEC) proliferation as well as chemotactic motility, and when we treated HUVEC cell with harmine, the formation of capillary-like structures was also restrained. Moreover, harmine induced bladder cancer cell apoptosis through triggering the caspase-dependent apoptotic pathway and the downstream vascular endothelial growth factor receptor 2 (VEGFR2) kinase pathway was down-regulated, thus suppressing tumor development signals. Herein, our study demonstrated that natural product harmine might have potential in curing human bladder tumor because of its pharmacological function on tumor angiogenesis, trigged by VEGFR2 signaling pathways.

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