A rapid assay for drug sensitivity of glioblastoma stem cells

被引:25
作者
Gal, Hilah
Makovitzki, Arik
Amariglio, Ninette
Rechavi, Gideon
Ram, Zvi
Givol, David [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
[2] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel
[3] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel
[4] Tel Aviv Univ, Sackler Fac Med, Dept Pediat Hematooncol, Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel
[5] Tel Aviv Med Ctr & Sch Med, Dept Neurosurg, Tel Aviv, Israel
关键词
neurospheres; 96-well plate; gleevec; DAPT; drug sensitivity;
D O I
10.1016/j.bbrc.2007.05.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu M). 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. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:908 / 913
页数:6
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