Andrographolide Inhibits Angiogenesis by Inhibiting the Mir-21-5p/TIMP3 Signaling Pathway

Int J Biol Sci. 2017 May 16;13(5):660-668. doi: 10.7150/ijbs.19194. eCollection 2017.

Abstract

Angiogenesis provides nutrients and oxygen to promote tumor growth and affords a channel that facilitates tumor cell entry into the circulation. Andrographolide (Andro) possess anti-tumor activity; however, its direct effect on angiogenesis still needs to be clarified. In this study, our experiments revealed that Andro significantly inhibited vascular growth in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumor angiogenesis was also suppressed by Andro. Additionally, we found that cell proliferation, migration and tube formation of vascular endothelial cells was inhibited by Andro treatment in vitro. The effect was primarily mediated through inhibition of miR-21-5p expression and further targeting of TIMP3. This work provides evidence that Andro directly inhibits angiogenesis and might be an effective anti-angiogenic therapeutic drug for cancer treatment.

Keywords: Andrographolide; TIMP3.; angiogenesis; miR-21-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane / drug effects
  • Chorioallantoic Membrane / metabolism
  • Diterpenes / pharmacology*
  • MicroRNAs / genetics*
  • Signal Transduction / drug effects
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism*

Substances

  • Diterpenes
  • MicroRNAs
  • Tissue Inhibitor of Metalloproteinase-3
  • andrographolide