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Mechanisms of Jzu4Me, a novel inhibitor of vascular endothelial growth factor induced angiogenesis and tumor angiogenesis
Author(s) -
Huang ShiuWen,
Huang TurFu
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.824.1
Subject(s) - angiogenesis , neovascularization , matrigel , vascular endothelial growth factor , cancer research , hif1a , microbiology and biotechnology , endothelial stem cell , vascular endothelial growth factor a , biology , chemistry , in vitro , biochemistry , vegf receptors
Background Angiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells. It plays a critical role in the growth and spread of cancer, due to the new vessels supply of oxygen and nutrients for tumors to grow, allowing the cancer cells to invade nearby tissue, leading to tumor metastases. Therefore, novel effective therapeutic agents of anti‐angiogenesis are greatly needed. Further studies established that vascular endothelial growth factor (VEGF)‐A is an attractive anti‐angiogenesis target for therapeutic interventions in cancer. Material and methods In an effort to develop inhibitors to block VEGF signaling and angiogenesis, benzimidazole derivatives were designed and synthesized, and their angiogenesis inhibitory effects both in vitro and in vivo were evaluated. Results Among these benzimidazole derivatives, Jzu4Me significantly inhibited VEGF‐A‐induced endothelial cells proliferation, migration, invasion and tubular formation, and it also suppressed ex vivo microvessels formation of rat aorta ring induced by VEGF‐A. Moreover, in Matrigel plug implantation mice, Jzu4Me dose‐dependently suppressed the VEGF‐A or tumor‐induced neovascularization in vivo. We also found that Jzu4Me may suppress VEGF‐A signaling in modulating vascular endothelial cell remodeling. Conclusions Our findings reveal that Jzu4Me inhibits VEGF‐induced angiogenesis via downregulation of VEGFR2‐mediated signaling, suggesting that Jzu4Me has high potential to be developed into a novel therapeutic agent for treating angiogenesis.