Artikel
Combination treatment of tumor treating fields and irradiation in human glioblastoma cells – does the temporal sequence make a difference?
Kombination von Tumor Treating Fields und Radiotherapie in humanen Glioblastomzellen – spielt die zeitliche Reihenfolge eine Rolle?
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Autoren
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Hanna Goett
- Justus-Liebig-Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Pia Sophie Salvers
- Justus-Liebig Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Alexandra Jensen
- Justus-Liebig Universität Gießen, Klinik für Strahlentherapie, Gießen, Deutschland
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Malgorzata A. Kolodziej
- Justus-Liebig Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Eberhard Uhl
- Justus-Liebig Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Marco Stein
- Justus-Liebig Universität Gießen, Klinik für Neurochirurgie/Zentrum für Neuroonkologie, Gießen, Deutschland
| Veröffentlicht: | 4. Juni 2021 |
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Gliederung
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Objective: Recent studies are investigating the concurrent application of tumor treating fields (TTFields) during radiochemotherapy in glioblastoma (GBM) patients. An influence on the repair mechanisms after irradiation (IR) in GBM cell lines in vitro was described, when TTFields were applied after IR. Nevertheless, whether TTFields have radiosensitizing effects on human GBM cells, when applied before IR, is an important question. The aim of our study is to compare the effects on cell proliferation when TTFields were applied before and after IR.
Methods: A172 and U87 GBM cells were plated on cover slips. After 24 hours one group received photon-beam IR at a dose of 4Gy and immediately afterwards TTFields at a frequency of 200Hz and a field intensity of 1.26 V/cm for 24 hours. The other group received the same treatment combination in the reverse order. 24h after treatment cells were harvested, and survival fractions (SF) were determined performing automatic cell count and clonogenic cell assays.
Results: IR alone decreased the number of surviving cells to 30.09% (95% CI: ±13.42%) in U87 cells and to a survival fraction of 34.57% (95% CI: ±8.66%) in A172 cells. After 24 hours treatment with TTFields alone U87 cells showed a survival fraction of 48.35 (95% CI: ±43.01%) while in A172 46.97% (95% CI: ± 16.57%) of cells were still viable. The survival rates after TTField treatment followed by IR were 33.5% (95% CI: ± 19.82%) in U87 and 26.56% (95% CI: ± 7.26%) in A172 cells. When IR was applied before TTFields 17.27% (95% CI: ± 9.82%) of U87 and 15.96% (95% CI: ± 2.48%) of A172 cells were counted as viable.
Conclusion: IR and TTFields treatment alone showed antiproliferative results on human GBM cells. The treatment with TTFields before IR had an additive effect on the survival of both GBM cell lines. However, only the sequence of IR followed by TTFields reached the cutoff for a synergistic effect in A172 cells and almost in U87 cells. These results imply that TTFields have an impact on the repair mechanisms after IR and a radiosenzitizing effect.
