A quantitative microfluidic angiogenesis screen for studying anti-angiogenic therapeutic drugs. Issue 1 (5th November 2014)

• Record Type: Journal Article
• Authors: Kim, Choong; Kasuya, Junichi; Jeon, Jessie; Chung, Seok; Kamm, Roger D.
• Is Part Of: Lab on a chip. Volume 15:Issue 1(2015)
• Page Start: 301
• Page End: 310
• Publication Date: 2014-11-05
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/c4lc00866a
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : Anti-angiogenic therapy is now widely accepted as a treatment for cancer. We introduce a new microfluidic platform that can monitor and quantify cellular behaviors, such as morphological changes, endothelial cell viability, and formation of angiogenic sprouts, depending on the various concentrations of drug applied (i.e., bortezomib, a selective 26S proteasome inhibitor). 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.