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 Citations (Scopus)

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

Fingerprint

Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor A
Endothelial Cells
Chorioallantoic Membrane
Cell Hypoxia
Neoplasms
Angiogenesis Inhibitors
Mitogen-Activated Protein Kinase Kinases
MCF-7 Cells
Microvessels
Heterografts
Microtubules
Chickens
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

ZLM-7 exhibits anti-angiogenic effects via impaired endothelial cell function and blockade of VEGF/VEGFR-2 signaling. / Su, Min; Huang, Jingjia; Li, Jijia; Qin, Xiyuan; Tang, Xiaoning; Jin, Fang; Chen, Shali; Jiang, Chuanming; Zou, Zizheng; Peng, Kunjian; Nuruzzaman, Mohammed; Zhang, Jian-Ting; Luo, Junli; Liu, Suyou; Luo, Zhiyong.

In: Oncotarget, Vol. 7, No. 14, 01.01.2016, p. 19018-19030.

Research output: Contribution to journalArticle

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, vol. 7, no. 14, pp. 19018-19030. https://doi.org/10.18632/oncotarget.7968
Su, Min ; Huang, Jingjia ; Li, Jijia ; Qin, Xiyuan ; Tang, Xiaoning ; Jin, Fang ; Chen, Shali ; Jiang, Chuanming ; Zou, Zizheng ; Peng, Kunjian ; Nuruzzaman, Mohammed ; Zhang, Jian-Ting ; Luo, Junli ; Liu, Suyou ; Luo, Zhiyong. / ZLM-7 exhibits anti-angiogenic effects via impaired endothelial cell function and blockade of VEGF/VEGFR-2 signaling. In: Oncotarget. 2016 ; Vol. 7, No. 14. pp. 19018-19030.
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AU - Tang, Xiaoning

AU - Jin, Fang

AU - Chen, Shali

AU - Jiang, Chuanming

AU - Zou, Zizheng

AU - Peng, Kunjian

AU - Nuruzzaman, Mohammed

AU - Zhang, Jian-Ting

AU - Luo, Junli

AU - Liu, Suyou

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