A quantitative microfluidic angiogenesis screen for studying anti-angiogenic therapeutic drugs
Author(s)Kim, Choong; Kasuya, Junichi; Jeon, Jessie S; Chung, Seok; Kamm, Roger Dale
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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.
Royal Society of Chemistry (Great Britain)
Kim, Choong, Junichi Kasuya, Jessie Jeon, Seok Chung, and Roger D. Kamm. “A Quantitative Microfluidic Angiogenesis Screen for Studying Anti-Angiogenic Therapeutic Drugs.” Lab Chip 15, no. 1 (2015): 301–310. doi:10.1039/c4lc00866a.
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