Indirubin inhibits tumor growth by antitumor angiogenesis via blocking VEGFR2-mediated JAK/STAT3 signaling in endothelial cell

Int J Cancer. 2011 Nov 15;129(10):2502-11. doi: 10.1002/ijc.25909. Epub 2011 Apr 7.


Tumor angiogenesis is one of the hallmarks of the development in malignant neoplasias and metastasis. Many angiogenesis inhibitors are small molecules from natural products. Indirubin, the active component of a traditional Chinese herbal medicine, Banlangen, has been shown to exhibit antitumor and anti-inflammation effects. But its roles in tumor angiogenesis, the key step involved in tumor growth and metastasis, and the involved molecular mechanism is unknown. Here, we identified that indirubin inhibited prostate tumor growth through inhibiting tumor angiogenesis. Using chick chorioallantoic membrane (CAM) assay and mouse corneal model, we found that indirubin inhibited angiogenesis in vivo. We also showed the inhibition activity of indirubin in endothelial cell migration, tube formation and cell survival in vitro. Furthermore, indirubin suppressed vascular endothelial growth factor receptor 2-mediated Janus kinase (JAK)/STAT3 signaling pathway but had little effects on the activity of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase in endothelial cell. Our study provided the first evidence for antitumor angiogenesis activity of indirubin and the related molecular mechanism. Our investigations suggested that indirubin was a potential drug candidate for angiogenesis related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Endothelial Cells / metabolism*
  • Humans
  • Indoles / pharmacology
  • Janus Kinases / metabolism
  • Male
  • Mice
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / drug therapy
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Xenograft Model Antitumor Assays


  • Angiogenesis Inhibitors
  • Antibiotics, Antineoplastic
  • Indoles
  • STAT3 Transcription Factor
  • Vascular Endothelial Growth Factor Receptor-2
  • Janus Kinases
  • indirubin