Abstract

Abstract OBJECTIVE Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The optimal combination therapy for Tumor Treating Fields (TTFields) in glioblastoma (GBM) treatment is unknown. The aim of our study was to analyze, the effects of the TERT-inhibitor eribulin in combination with TTFields on human GBM cells. METHODS Human GBM cells of the established cell lines U87, A172 and U251, and two patient-derived cell lines, were treated with eribulin monotherapy, TTFields monotherapy, or both modalities together. After 72 hours of therapy, cell counts were measured and clonogenic assays were performed. Annexin staining and fluorescence-activated cell scanning (FACS) was used to analyze cell death. RESULTS Overall surviving fractions were 39.8±11.0% for eribulin monotherapy, 32.2±23.9% for TTFields monotherapy, and 10.9±9.9% for the combined treatment. Mean observed annexin positive fractions were 11.2±8.2% (control), 28.6±9.7% (eribulin), 34.8±8.1% (TTFields), and 78.1±13.5% (combination), respectively. The mean clonogenic fractions over all cell lines were 25.9±7.8% for eribulin and 46.4±12.9% for TTFields. For the combination therapy, a synergistic effect with a decreased mean of 3.6% clonogenic fractions was observed. CONCLUSION Eribulin increases cell death and reduces clonogenicity our experiments. Additionally, a synergistic effect of the combined treatment of TTFields and eribulin synergistic was observed. Eribulin in combination with TTFields could be a new effective therapy for GBM.

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