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Information × Registration Number 0225U002306, (0121U113838) , R & D reports Title The role of lactate dehydrogenase in the survival and desemination of metastatically active cells (2.2.5.443) popup.stage_title Проаналізувати зміни показників виживаності та метаболічної пластичності в метастатично активних клітинах за умов переходу з адгезивного (на фоні дефіциту глюкози та гіпоксії) в деадгезивний режим росту в недефіцитному за субстратами середовищі Head Solianyk Halyna I., Доктор фізико-математичних наук Registration Date 03-03-2025 Organization R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology National Academy of Sciences of Ukraine popup.description1 To study the influence of the metabolic microenvironment, associated with the different stages of the metastatic cascade, on the survival rate and energy metabolism parameters of metastatically active cells and to reveal the role of LDH in the ability of these cells to adapt under variable survival conditions popup.description2  Metastasis of malignant tumors is critically dependent on the ability of metastatic cells to survive during detachment from the extracellular matrix in the primary tumor and transition to deadhesive growth upon dissemination. The work at stage 2024 aimed to investigate the effect of nutrient substrate deficiency on the sensitivity of metastatic Lewis lung carcinoma (LLC) cells to anoikis. Substrate-deficient growth conditions for adhesive LLC cells were created using glycolysis inhibitors (sodium oxamate and 2-deoxyglucose), the mitochondrial respiration inhibitor metformin, and their combinations. It has been proven that combinations of oxamate with metformin and 2-deoxyglucose with metformin in relatively low concentrations cause, on the one hand, a significant cytotoxic effect on LLC cells during their adhesive growth, and on the other hand, significantly increase the sensitivity of these cells to anoikis, reducing their survival rate several times during the transition to deadhesive growth. In contrast to the combined effect, all three energy metabolism inhibitors in higher concentrations (compared to the combined effect) exhibit a 2-fold lower cytotoxic effect on adhesive cells and weaken the sensitivity of cells to anoikis. It has also been shown that combinations of glycolysis inhibitors with metformin cause an antitumor form of polarization of peritoneal macrophages of animals with LLC in contrast to the action of glycolysis inhibitors, which promote proangiogenic polarization of macrophages with the ability to stimulate the tumor process. Product Description popup.authors Kolesnyk Denys L. Prokhorova Iryna V. Stepanov Yurii V. Yakshybaieva Yuliia R. popup.nrat_date 2025-03-03 Close