P11.14 The addition of hyperbaric oxygen to the treatment of T98G glioblastoma cell cultures with selected CK2 inhibitor TDB enhances its anti-tumour effect

Abstract

Abstract BACKGROUND Glioblastoma (GBM) is the most aggressive glial neoplasm characterized by infiltrative cell growth in adults. The current standard of care for high-grade glioma patients includes surgery, radiotherapy and chemotherapy using temozolomide and other alkylating agents. Despite this, median survival of the patients with GBM is less than two years. One of the main factors related to the progression of neoplastic cells is hyperactivity of protein kinases, including CK2 kinase and a high level of tumor hypoxia, both of which also contribute to tumour resistance to treatment. Our previous study indicated that some CK2 inhibitors exhibit anti-proliferative effect on glioma cells. The aim of this study was to examine whether HBO may enhance the anti-tumour efficacy of 1-(β-D-2’-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole (TDB) - CK2 inhibitor, under combination HBO/TDB therapy. MATERIAL AND METHODS Studies were performed on human glioblastoma T98G cell line (ATCC). Cells were cultured in MEM medium supplemented with 1-(β-D-2’-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole in concentrations of 0.1 μM; 1 μM, 25 μM, 50 μM, 75μM, 100 μM. Cultures were sustained in various oxygen conditions: normoxia for 24 and 48 hours or1 hour of hyperbaric oxygen (HBO, 97,5% O2/2,5% CO2, pressure of 2 ATA) followed by 23 hours of normoxia (21% O2/5% CO2/78% N2). Control groups included the cultures sustained in normoxia conditions. The viability of glioma cell lines was established at 24 and 48 hours post TDB treatment by Cell Titer 96®A Queous One Solution Cell Proliferation Assay. RESULTS The study evidenced that TDB inhibited the viability of neoplastic cells at a concentration of 75 μM after 24 and 48 hours. Administration of hyperbaric oxygen alone also caused a reduction in viability of glioblastoma cells. The cytotoxic effect of the tested CK2 inhibitor was significantly enhanced when tested compound was combined with HBO. What’s more, under the influence of hyperbaric oxygen, TDB significantly reduced the viability of tumor cells already at a concentration of 25 μM after 24 hours. CONCLUSIONS Hyperbaric oxygen administration significantly reduces the viability of T98G line cells and increases their sensitivity to the tested CK2 kinase inhibitor. The beneficial cytotoxic effect of TDB/HBO can be obtained at lower concentrations of the tested compound and after shorter exposure time as compared to its administration without HBO. Acknowledgement: The research was supported by the Foundation for the Development of Diagnostic and Therapy, Warsaw