TMIC-38. ENHANCED EFFICACY OF TUMOR TREATING FIELDS AND AURORA B KINASE INHIBITOR COMBINATION IN GLIOMA CELL LINES

Abstract

Tumor Treating Fields (TTFields) are anti-mitotic, low intensity, intermediate frequency, alternating electric fields approved for glioblastoma. The efficiency of TTFields may be enhanced by drugs that extend metaphase-anaphase transition and telophase such as Aurora B kinase. We studied if TTFields’ effect on tumor cells is enhanced by additional inhibition of cytokinesis through Aurora B kinase. TTFields and Aurora B kinase inhibitors (AZD1152) combination was tested in glioma cell lines: in U87-MG, U87-MGshP53 and U-251, and U87-MG, first and then in two primary glioblastoma cell lines (HT16360, HT18503). TTFields (1.6 V/cm RMS, 200 kHz) were applied for 72 hours using the inovitro system. AZD1152 was added up to 100 nmol/L. Cell counts, cell cycle and clonogenic potential were determined. Multinuclear cells formation was determined using crystal violet staining. TTFields and AZD1152 combination led to a significant reduction in the number of U251, U-87 MG and U-87 MGshP53 cells (2-way ANOVA, pshP53 and U-251 cells (2-way ANOVA, pshP53 cells stained with crystal violet after treatment revealed high prevalence of multi nuclear cells in cells exposed to TTFields and AZD1152 (25nM) versus AZD1152 (25nM) alone. Cells treated with TTFields and higher doses of AZD1152 (50-100nM) demonstrated increased rates of pyknosis. Data could be confirmed in primary tumor-cell lines. These results demonstrate that combining TTFields and AZD1152 can be an effective treatment in glioma. There is a strong rational to continue exploring the potential of combining TTFields and AZD1152 in the clinical settings.