期刊
LAB ON A CHIP
卷 15, 期 1, 页码 301-310出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4lc00866a
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资金
- US National Institutes of Health [R33 CA174550]
- National Science Foundation [CBET-0939511]
- National Research Foundation of Korea [2012-0009565, 2014M3A7B4052193]
- Ministry of Trade, Industry & Energy of Korea [20124010203250]
- Kyungil University
- NATIONAL CANCER INSTITUTE [R33CA174550] Funding Source: NIH RePORTER
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.
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