A quantitative microfluidic angiogenesis screen for studying anti-angiogenic therapeutic drugs

Lab Chip. 2015 Jan 7;15(1):301-10. doi: 10.1039/c4lc00866a.


Anti-angiogenic therapy, which suppresses tumor growth by disrupting oxygen and nutrient supply from blood to the tumor, is now widely accepted as a treatment for cancer. To investigate the mechanisms of action of these anti-angiogenesis drugs, new three dimensional (3D) cell culture-based drug screening models are increasingly employed. However, there is no in vitro high-throughput screening (HTS) angiogenesis assay that can provide uniform culture conditions for the quantitative assessment of physiological responses to chemoattractant reagents under various concentrations of anti-angiogenesis drugs. Here we describe a method for screening and quantifying the vascular endothelial growth factor (VEGF)-induced chemotactic response on human umbilical vein endothelial cells (HUVECs) cultured with different concentrations of bortezomib, a selective 26S proteasome inhibitor. With this quantitative microfluidic angiogenesis screen (QMAS), we demonstrate that bortezomib-induced endothelial cell death is preceded by a series of morphological changes that develop over several days. We also explore the mechanisms by which bortezomib can inhibit angiogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods
  • Neovascularization, Pathologic*
  • Pyrazines / pharmacology
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inhibitors
  • Boronic Acids
  • Pyrazines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bortezomib