Artikel
The combination therapy of tumour treating fields with the TERT-inhibitor eribulin shows synergistic antiproliferative effects on human glioblastoma cells
Die Kombinationstherapie von Tumor Treating Fields mit dem TERT-Inhibitor Eribulin zeigt synergistische antiproliferative Effekte an humanen Glioblastomzellen
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Veröffentlicht: | 4. Juni 2021 |
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Objective: Treatment of glioblastoma (GBM) is challenging. Past milestones in the therapy were the addition of radiation therapy with temozolomide (TMZ), and the treatment with Tumor Treating Fields (TTFields) during TMZ maintenance. The aim of the study was to analyze, for the first time, the effects of the TERT-inhibitor eribulin in combination with TTFields on cell death and clonogenicity of human GBM.
Methods: Human GBM cells of the established cell lines U87, A172 and U251, as well as two patient-derived cell lines (447 and 455), were treated with eribulin, TTFields, or both modalities. After 72 hours of therapy, cell counts were measured. Additionally, clonogenic assays were performed. Cell death was analyzed using annexin V staining and fluorescence-activated cell scanning (FACS). The mean differences between cell counts, clonogenic fractions and FACS were evaluated.
Results: The mean surviving fractions over all cell lines (Figure 1 [Fig. 1]) were 42.6±SD % for eribulin, 35.7±% for TTFields, and 15.2±SD% for the combination. The mean annexin positive fractions over all cell lines were 12.8±SD% (control), 30.1±SD% (eribulin), 35.3±% (TTFields), and 75.5±SD% (combination), respectively. The mean clonogenic fractions over all cell lines (Figure 2 [Fig. 2]) were 19.1±SD% for eribulin and 33.6±SD% for TTFields. In the combination therapy, synergistic effects with a decreased mean of 3.2±SD% clonogenic fractions were observed.
Conclusion: Eribulin increases cell death and reduces clonogenicity in human GBM cells. Furthermore, for the combined treatment of TTFields and eribulin synergistic effects on cell proliferation were observed. Our data highlight the therapeutic potential of eribulin used in combination with TTFields and offer important insights for possible new effective GBM therapies.