Gal Hilah, Makovitzki Arik, Amariglio Ninette, Rechavi Gideon, Ram Zvi, Givol David
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Biochem Biophys Res Commun. 2007 Jul 6;358(3):908-13. doi: 10.1016/j.bbrc.2007.05.020. Epub 2007 May 11.
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 microM). 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.
胶质母细胞瘤（GBM）是一种具有高度浸润性的侵袭性脑癌，目前尚无有效的治愈性治疗方法。我们开发了一种快速检测方法，用于评估各种药物对GBM干细胞的作用。该检测方法在96孔板中使用少量分离的CD133 +细胞（0.2 ml中含20,000个），这些细胞在1 - 2天内形成神经球。各种药物在24 - 36小时内使神经球分散，这可以通过显微镜进行定量。我们使用GBM细胞系A - 172来确定该检测方法的条件，使用了格列卫、γ-分泌酶抑制剂DAPT和抗菌肽amph1D。结果显示，在相对较低的药物浓度（<25 microM）下，神经球分散导致细胞死亡。药物组合在较低浓度下显示出协同作用并破坏神经球。我们将该检测方法应用于三名患者手术标本的CD133 +细胞，结果相似。该检测方法有助于对少量分级分离的患者GBM干细胞进行快速药物测试。
