ZLM-7 exhibits anti-angiogenic effects via impaired endothelial cell function and blockade of VEGF/VEGFR-2 signaling

Min Su, Jingjia Huang, Jijia Li, Xiyuan Qin, Xiaoning Tang, Fang Jin, Shali Chen, Chuanming Jiang, Zizheng Zou, Kunjian Peng, Mohammed Nuruzzaman, Jianting Zhang, Junli Luo, Suyou Liu, Zhiyong Luo

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Inhibition of angiogenesis is a promising therapeutic strategy against cancer. In this study, we reported that ZLM-7, a combretastain A-4 (CA-4) derivative, exhibited anti-angiogenic activity in vitro and in vivo. In vitro, ZLM-7 induced microtubule cytoskeletal disassembly. It decreased VEGF-induced proliferation, migration, invasion and tube formation in endothelial cells, which are critical steps in angiogenesis. In vivo, ZLM-7 significantly inhibited neovascularization in a chicken chorioallantoic membrane (CAM) model and reduced the microvessel density in tumor tissues of MCF-7 xenograft mouse model. ZLM-7 also displayed comparable antiangiogenic and anti-tumor activities associated with the lead compound CA-4, but exhibited lower toxicity compared with CA-4. The anti-angiogenic effect of ZLM-7 was exerted via blockade of VEGF/VEGFR-2 signaling. ZLM-7 treatment suppressed the expression and secretion of VEGF in endothelial cells and MCF-7 cells under hypoxia. Further, ZLM-7 suppressed the VEGF-induced phosphorylation of VEGFR-2 and its downstream signaling mediators including activated AKT, MEK and ERK in endothelial cells. Overall, these results demonstrate that ZLM-7 exhibits anti-angiogenic activities by impairing endothelial cell function and blocking VEGF/VEGFR-2 signaling, suggesting that ZLM-7 might be a potential angiogenesis inhibitor.

Original languageEnglish (US)
Pages (from-to)19018-19030
Number of pages13
JournalOncotarget
Volume7
Issue number14
DOIs
StatePublished - Jan 1 2016

Keywords

  • Angiogenesis
  • Microtubule
  • VEGF
  • VEGFR2
  • ZLM-7

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'ZLM-7 exhibits anti-angiogenic effects via impaired endothelial cell function and blockade of VEGF/VEGFR-2 signaling'. Together they form a unique fingerprint.

  • Cite this

    Su, M., Huang, J., Li, J., Qin, X., Tang, X., Jin, F., Chen, S., Jiang, C., Zou, Z., Peng, K., Nuruzzaman, M., Zhang, J., Luo, J., Liu, S., & Luo, Z. (2016). ZLM-7 exhibits anti-angiogenic effects via impaired endothelial cell function and blockade of VEGF/VEGFR-2 signaling. Oncotarget, 7(14), 19018-19030. https://doi.org/10.18632/oncotarget.7968