Antiangiogenic properties of caudatin in vitro and in vivo by suppression of VEGF‑VEGFR2‑AKT/FAK signal axis

caudatin 通过抑制 VEGF‑VEGFR2‑AKT/FAK 信号轴在体内和体外表现出抗血管生成特性

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作者:Xinzhi Wang, Xiaoting Fu, Shijun Zhao, Xiaoyan Fu, Huifang Zhang, Lurong Shao, Gang Li, Cundong Fan

Abstract

Tumor angiogenesis provides essential nutrients and oxygen to the tumor microenvironment, which is important in tumor growth, progression and metastasis. Inhibition of tumor angiogenesis represents one of the most promising strategies in tumor therapy. The authors previously demonstrated that caudatin, one species of C‑21 steroidal from Cynanchum auriculatum (C. auriculatum), effectively inhibits human glioma growth in vitro and in vivo through triggering cell cycle arrest and apoptosis. However, little information regarding the antiangiogenic properties of caudatin in human glioma is available. Based on the author's previous study, the antiangiogenic effect of caudatin against human glioma was explored, and the underlying mechanism was investigated. The results suggested that caudatin treatment significantly inhibited HUVEC human umbilical vein endothelial cell proliferation, blocked the HUVECs migration, invasion and capillary‑like tube formation by disturbing the vascular endothelial growth factor (VEGF)‑VEGFR2‑protein kinase B (AKT)/focal adhesion kinase (FAK) signal axis. Notably, caudatin treatment abolished the glioma cell growth by suppression of the in vivo angiogenesis, which involved FAK and AKT dephosphorylation and inhibition of VEGF expression. The findings validated the antiangiogenic potential of caudatin in hunting human glioma.

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