Article
The effect of a novel Aurora-A kinase inhibitor in combination with tumour treating fields and temozolomide on glioblastoma cells
Die Wirkung eines neuartigen Aurora-A-Kinase-Inhibitors in Kombination mit Tumortherapiefeldern und Temozolomid auf Glioblastomzellen
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Authors
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Kseniia Novikova
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
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Susanne Michen
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
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Katja Robel
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
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Achim Temme
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
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Dietmar Krex
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Tumor Treating Fields (TTFields) have been shown to be effective in prolonging progression-free and overall survival in patients with primary glioblastoma and increasing the rate of two- and five-year survivors. Nevertheless, there is an urgent need to further improve survival data. A promising approach is to combine this kind of treatment with drugs that enhance the biological effect of TTFields. In the present in vitro study, we tested the efficacy of a novel selective inhibitor of Aurora A kinase, VIC-1911, in combination with TTFields and temozolomide (TMZ) in primary glioblastoma cells.
Methods: We used the inovitro® system to apply TTFields (1.7 V/cm RMS, 200 kHz) to three primary glioblastoma cell lines. The suitable effective dose of VIC-1911 and TMZ was titrated and then used for combination treatment. The cytotoxic effect was determined by flow cytometry analysis of living cells. In addition, ploidy was evaluated and morphological changes of the treated cells were visualized by light and fluorescence microscopy.
Results: We found that the combination of TTFields plus VIC-1911 and TMZ had a significantly cytoreductive effect that was stronger than that of the single treatments and depending on the cell line of the double treatments. In addition, we showed an increased DNA content in PI-stained glioblastoma cells suggesting polyploidy and disturbed cell replication after the combination treatment with treatment with TTFields and VIC-1911, TTFields and TMZ, or TTFields plus VIC-1911 and TMZ compared to the single treatments. Both, light and fluorescence microscopy, showed an increase in morphological changes such as multinucleated cells, enlarged cells, as well as cytoskeletal modifications.
Conclusion: In the present study we demonstrated that the novel Aurora-A kinase inhibitor VIC-1911 is a suitable drug to enhance effect of TTFields on primary glioblastoma cells. However, further studies are needed to find the optimal dose for combination treatment with TMZ.
