The prolonged hyperbaric oxygen as a component of the combination therapy with CK2 kinase inhibitors against malignant glioma cells in vitro.

Treatment options for glioblastoma remain limited and unfortunately even with maximal resection and postoperative adjuvant treatments, the median overall survival of patients remains approximately 15 months. In the present study we investigated the effect of HBO (2ATA - atmospheres absolute) prolonged to 2 hours on antitumor efficacy of selected CK2 kinase inhibitors in two distinct human malignant glioma cell lines, T98G and U87MG. Tested compounds were administered in increasing concentrations within the range of 5-100µM either under normoxia or with the addition of HBO at the beginning of experiments. After 24 hour incubation, 2 hour HBO decreased the viability of T98G cells in response to CK2 kinase inhibitors 2-aminoetylo-amino-4,5,6,7-tetrabromo-1H-benzimidazol (TBIAEA), 2/ 4,5,6,7-tetrabromoN²metylo-N²hydroksyetylo 2 ami-nobenzimidazol (TMHA), and 3/ 1-(β-D-2'-deoxy-ribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazol(TDB), as compared to treatments with these inhibitors under normoxia. The 2 hour HBO-induced reductions of viability amounted up to 36% over pharmaceutics alone and occurred at 5-100µM of their concentration range. Notably, as compared with 1 hour HBO sessions combined with CK2 kinase inhibitors, 2 hour HBO sessions combined with these pharmaceuticals produced greater reductions of viability of T98G cells, resulting in the lowest numbers of surviving tumor cells in the whole experiment. In T98G cells, as compared with U87MG cells, 2 hour HBO caused more potent reductions over pharmaceuticals alone. Thus, the prolonged dosing of HBO may increase tumoricidal effect of antiglioma agents and hence deserves further study. Investigating even more prolonged HBO exposures and other kinase inhibitors combined with HBO against glioblastoma cells would be worth a while. This work was supported by the Foundation for Development of Diagnostic and Therapy Warsaw. [ABSTRACT FROM AUTHOR]