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Registration Number

0224U002898, 0121U113838 , R & D reports

Title

The role of lactate dehydrogenase in the survival and desemination of metastatically active cells (2.2.5.443)

Head

Solianyk Halyna I., Доктор фізико-математичних наук

Registration Date

12-03-2024

Organization

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology National Academy of Sciences of Ukraine

Description

To achieve the goal, an experimental model (using highly metastatic Lewis lung carcinoma cells) of intravasation of metastatically active cells from the hypoxic tumor microenvironment to normoxic and energy-substrate-enriched circulation conditions in the bloodstream was developed. It has been proven that hypoxia does not significantly affect the survival and proliferative activity of metastatic cells during the transition to deadhesive growth, which indicates a high oxygen-independent level of their resistance to anoikis. This is due to the high metabolic plasticity of these cells, which is manifested in a significant increase in glucose consumption rate and a significant increase in the number of mitochondria during deadhesive growth. Studies of the effect of lactate dehydrogenase inhibitor oxamate and hexokinase-1 inhibitor 2-deoxyglucose proved their high cytotoxic activity against deadhesive metastatic cells in comparison with the cytotoxic effect of the inhibitor of oxidative phosphorylation oligomycin. The conducted studies showed that the inhibition of various links of glycolysis (compared to the inhibition of oxidative phosphorylation) in circulating metastatic cells is a more promising strategy for antimetastatic therapy.

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Kolesnyk Denys L.
Prokhorova Iryna V.
Stepanov Yurii V.
Yurchenko Olha V.
Yakshybaieva Yuliia R.