Evaluation of the Antitumoral Effect of PI3K/AKT/mTOR Pathway Inhibition and Antioxidant Combination on Burkitt Lymphoma Cell Line.
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BACKGROUND AND AIM: Burkitt lymphoma is a highly aggressive type of B-cell non-Hodgkin lymphoma. While it is more commonly seen in children and adolescents, it accounts for about 1-2% of adult lymphomas. Since it has high Ki-67 ratios, both its progression rate and sensitivity to chemotherapy are high. However, treatment success decreases in chemotherapy-resistant relapsed/refractory groups. Therefore, new and less toxic therapeutic agents targeting biological pathways related to Burkitt lymphoma pathogenesis are needed. In our study, we aimed to determine the antitumoral efficacy of PI3K/AKT/mTOR pathway inhibitor ETP 45658 and antioxidant Resveratrol, which play a role in Burkitt lymphoma pathogenesis on a Burkitt lymphoma cell line. METHODS: Burkitt lymphoma Raji cell line was used in our study. ETP 45658 was applied to the cell line at concentrations of 50, 25, 12.5, 1, 0.1, and 0.01 μM, both alone and in combination with 100 μM resveratrol. The cytotoxic effects of ETP 45658 and the combination treatment on Raji cells were then evaluated using an in vitro XTT cell viability test. IC50 value was calculated according to the results obtained in the XTT test. Based on the IC50 value, the apoptosis assay was studied using the flow cytometry method. RESULTS: Our research showed that increasing doses of ETP 45658, individually and in combination, had a statistically significant cytotoxic effect on Burkitt lymphoma Raji cells. This cytotoxic effect was found to be higher in combination treatment. In apoptosis experiments with the calculated IC50 value, it induced apoptosis weakly. CONCLUSION: Our study showed that ETP 45668 alone and in combination with resveratrol has antitumoral activity on the Burkitt lymphoma cell line. PI3K/Akt/mTOR pathway inhibitors may be an alternative treatment option in patients with relapsed/refractory Burkitt lymphoma. However, more preclinical and clinical studies are needed.