Abstract
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.
Original language | English |
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Pages (from-to) | 908-913 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 358 |
Issue number | 3 |
DOIs | |
State | Published - 6 Jul 2007 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank the Kahn Family Foundation for their support. This research was partially supported by the Wolfson Family Charitable Trust on Tumor Cell Diversity, by the Yad Abraham foundation and by a grant from Ruth & Allen Zeigler for Stem Cell research.
Keywords
- 96-Well plate
- DAPT
- Drug sensitivity
- Gleevec
- Neurospheres