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

Choong Kim, Junichi Kasuya, Jessie Jeon, Seok Chung, Roger D. Kamm

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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. This journal is

Original languageEnglish
Pages (from-to)301-310
Number of pages10
JournalLab on a Chip - Miniaturisation for Chemistry and Biology
Volume15
Issue number1
DOIs
Publication statusPublished - 2015 Jan 7

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)
  • Bioengineering
  • Biomedical Engineering

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