A rapid assay for drug sensitivity of glioblastoma stem cells

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• 作者：Hilah Gal ; Arik Makovitzki ; Ninette Amariglio ; Gideon Rechavi ; Zvi Ram ; David Givol
• 关键词：Neurospheres ; 96-Well plate ; Gleevec ; DAPT ; Drug sensitivity
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2007
• 出版时间：6 July 2007
• 年：2007
• 卷：358
• 期：3
• 页码：908-913
• 全文大小：1875 K

文摘

Glioblastoma (GBM) is a highly infiltrating, aggressive brain cancer with no available curative treatment. We developed a rapid assay for assessing the effect of various drugs on GBM stem cells. The assay uses a small number of separated CD133+ cells (20,000 in 0.2 ml) in 96-well plate that form neurospheres within 1–2 days. Various drugs disperse the neurospheres within 24–36 h, which can be quantified microscopically. We used the GBM cell line A-172 to develop the conditions for the assay, utilizing Gleevec, the gamma-secretase inhibitor DAPT, and the anti-bacterial peptide amph1D. The results show dispersion of the neurospheres leading to cell death, at relatively low drugs concentrations (<25 μM). Drug combination showed a synergistic effect and disruption of neurospheres under lower concentrations. We applied this assay to the CD133+ cells of surgical specimens from three patients that showed similar results. This assay facilitates a rapid test of drugs on small amounts of fractionated patient’s GBM stem cells.