Artikel
The sphingosine-1-phosphate analogon FTY720 has potent antiproliferative effects on glioblastoma cell line
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Autoren
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Malgorzata Kolodziej
- Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Giessen
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B. Al-Barim
- Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Giessen
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Marco Stein
- Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Giessen
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Marcus Reinges
- Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Giessen
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Eberhard Uhl
- Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Giessen
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K. Quint
- Pathologisches Institut, Universitätsklinikum Erlangen
| Veröffentlicht: | 21. Mai 2013 |
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Gliederung
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Objective: The sphingosine-1-phosphate (S1P) pathway is involved in cell survival, growth, migration and angiogenesis. While overexpressed in gliomas, we and others have previously shown the influence of sphingosne kinase 1 and S1P-receptor 1 expression on survival of glioma patients. Here we investigate the antiproliferative effects of the S1P analogon FTY720 (fingolimod) in glioblastoma cell lines.
Method: Glioblastoma cell lines A172, G28 and U87 were incubated with 5, 10, 25 and 50 µM FTY720 or temozolomide (TMZ) for 24 to 72 hours and proliferation was measured using an MTT assay and the xCELLigence system, an impedance-based cell proliferation and viability system. IC50 values for FTY720 were calculated at 72 hours and compared to TMZ effects.
Results: Within 24 hours 10 µM FTY720 already reduced viable A172 cells to less than 5% and after 72 hours 10 µM FTY720 reduced viable A172 cells to 2.3% of untreated controls. Similar dose-dependent results were obtained for G28 and U87 cells with viable cells below 2% at 72 hours using 50 µM FTY720. IC50 at 72 hours of FTY720 incubation was 4.6 µM in A172 cells, 17.3 µM in G28 and 25.2 µM in U87 cells, respectively. Its effects surpassed those of TMZ, which did not reduce viable cell counts below 50% in any cell line even at 50 µM.
Conclusions: FTY720 has strong antiproliferative effects on glioblastoma cells at micromolar concentrations and greatly surpasses TMZ effects. Therefore, it seems to be a promising targeted drug for this cancer.
