Molecular biological investigation of combinations of temozolomide and kc7f2 agents in glyoma cells

Brain tumors occupy an important place in neuronal diseases and are classified as I, II, III and IV by World Health Organization (WHO) based on their histological, invasive and genetic characteristics. Glioblastom Multiforme (GBM) is the most invasive and malignant member of the IV grade of the subclass Astrocytoma according to the last assessment of the 2016 WHO report. Due to the resistance to treatment and weak response, as well as the topographical structure of the blood brain barrier, which is a major part of malignant brain tumors, treatment is also difficult due to the severe clinical manifestation, and new treatment methods and new therapeutic agents are needed. Conventional treatment methods are surgical resection, radiotherapy and chemotherapy. Median survival time is 12.5 months in patients. Temozolomide (TMZ) is widely used in the treatment of glioblastoma and is considered as the primary treatment modality. TMZ, a member of the class of cognitive agents, is currently considered the most effective drug because it can easily pass through the blood brain barrier. However, when administered in combination with radiotherapy, the survival time does not exceed 15 months. The reason for this is the resistance mechanism against TMZ. Glucose metabolism is a complex energy producing machine that generates energy and stores it as ATP and provides energy for all cellular processes. A glucose molecule produces 38 molecules of ATP after full glycolytic catabolism. According to Otto Warburg's numerous studies and basic hypothesis, cancer metabolism is completely different from normal cells. Cancer cells tend to the anaerobic phenotype only by performing the first glycolytic step without entering the mitochondrial step. As a result, these cells produce lactic acid and make the secretions and micro-media even more acidic in aerobic conditions. This phenomenon is attributed to the Warburg hypothesis and either as anaerobic glucolysis. Although glycolysis enzymes are the primary actors of this phenotypic expression, some genetic and epigenetic factors are no exception. For this reason, we experimentally used KC7F2 active ingredient to target cancer metabolism. In our study, we evaluated cancer metabolism in combination with the effect of TMZ chemotherapeutic agent, examining the effect of two different agents separately and in combination to observe the effects of cancer cell proliferation, survival, apoptosis, expression of metabolism genes on expression. As a result of our experience, we observed that the combined effect of the active ingredients reduced the effective dose of the TMZ alkylating agent and that the effect was increased. We have also observed that the effect of the combined teraphy is assessed from a metabolic point of view and that it suppresses aerobic glycolysis.