Investigation of cytotoxic, apoptotic, and antiangiogeniceffects of ixazomib and fumagillin combination on glioma cells

In this study, we aimed to investigate the cytotoxic/synergistic, apoptotic and antiangiogenic effects of the combination of ixazomib and fumagillin on glioma cells. U87MG, SHSY-5Y and C6 glioma cell lines and HUVEC endothelial cells were used to evaluate their cytotoxic effects. Cytotoxic effects were determined by the MTT method and CDI values were calculated. Proliferation and migration effects of certain concentrations were studied in U87MG glioma cells in a real-time cell analysis system. Apoptotic effects were determined in glioma cells using the annexin V-PI method in cell flow cytometry. In single and combined applications of ixazomib and fumagillin, an increase in cytotoxic effect was found in all cell lines compared to the control, depending on the increase in concentration. According to CDI values, it was determined that combined applications had a synergistic effect at high concentrations, especially on HUVEC endothelial cells and U87MG and SHSY5Y glioma cells. Early apoptotic cell rates of ixazomib and fumagillin combination were observed at 5+50 μM in U87-MG cells; It was also observed to be present at 5+100 μM in SHSY-5Y cells. Single and combined application (5+50 μM) of Ixazomib (5μM) and Fumagillin (50 μM) inhibited cell proliferation in a time-dependent manner in the U87-MG cell line, and it was analyzed that these concentrations showed similar migration inhibitory effects compared to the control. In conclusion, we believe that understanding the synergistic/cytotoxic, apoptotic and antiangiogenic effects of ixazomib, a proteasome inhibitor, and fumagillin, an antifungal drug, on glioma glioma cells will contribute to the development of effective therapeutic approaches in glioma treatment.