STUDY OF ENERGY METABOLISM OF MALIGNANT CELLS: NEW HORIZONS FOR TARGETED THERAPY

Metabolic reprogramming is one of the key mechanisms ensuring the growth and survival of malignant cells. The phenomenon of increased glycolysis under aerobic conditions, known as the Warburg effect, plays an important role in the energy metabolism of tumor cells. Systematic study of energy metabolism of various tumor cultures in vitro remains an urgent task, as it contributes to understanding the mechanisms of regulation of cancer cell metabolism and may lead to the discovery of new therapeutic targets. The aim of the study: to investigate the energy metabolism of malignant cell (oxidative phosphorylation and glycolysis) by analyzing extracellular fluxes in an experimental model in vitro. Materials and methods: SeaHorse XFp automatic analyzer of extracellular fluxes was used to estimate the rate of oxygen uptake (OCR) and the rate of extracellular proton acidification (ECAR), characterizing the intensity of oxidative phosphorylation and glycolysis, respectively. HeLa cell culture (cervical adenocarcinoma) and human embryonic skin fibroblast culture as a control were investigated. Mitochondrial stress tests with the addition of respiratory chain uncouplers were performed to analyze cellular respiration defects. RESULTS: Oxidative phosphorylation rate (OCR) and glycolysis (ECAR) were significantly reduced in HeLa cell culture compared with control fibroblast culture. In addition, HeLa cells showed a reduced response to the administration of mitochondrial inhibitors compared to the normal fibroblast response. Conclusion: the data obtained may indicate the existence of an additional mode of energy production in HeLa tumor cell culture that allows cells to maintain viability and increase tumor mass. Further study of the energy metabolism of tumor cells may open new opportunities for the search of molecular biotargets and development of targeted drug therapy.