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, Jian-Ting Zhang, Junli Luo, Suyou Liu, Zhiyong Luo

Research output: Contribution to journalArticle

7 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
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Oncology

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-T., 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