The Effect of the Combinations of 5-Fluorouracil, Leptin and Leptin Antagonist in Glioblastoma ^†

Abstract

Glioblastoma (GB) is the most aggressive form of brain tumor and resistant to chemotherapy. New therapeutic approaches are needed to improve the efficacy of chemotherapy. It was reported that there may be a relationship between obesity and poor prognosis in GB treatment. However, there is no study investigating the relationship between leptin, leptin receptor and chemotherapy in GB. The aim of this study was to investigate the cytotoxic effects of 5-Fluorouracil (5-FU) in the treatment of GB in the presence of leptin and leptin receptor antagonist SHLA. LN-405, T98G and U373-MG GB cell lines were used for this purpose. The cytotoxic effects of these molecules in both single and combination were determined by MTT. The sensitivities of GB cell lines to 5-FU were found to be different and leptin and SHLA had no cytotoxic effects in GB cells. It was determined that leptin increased 5-FU toxicity by 8–57% depending on 5-FU dose and cell type in all three cell lines in combination groups. A similar effect was detected in combinations of SHLA with 5-FU (6–58%). This is the first study to show that combinations of 5-FU with leptin and SHLA increase the cytotoxicity of 5-fluorouracil in cancer.