Cancer Drug Resistance: Targeting Proliferation or Programmed Cell Death

Sazonova, E.V.; Yapryntseva, M.A.; Pervushin, N.V.; Tsvetcov, R.I.; Zhivotovsky, B.; Kopeina, G.S.

Авторы: Sazonova E.V., Yapryntseva M.A., Pervushin N.V., Tsvetcov R.I., Zhivotovsky B., Kopeina G.S.
Журнал: Cells
Том: 13
Номер: 5
Год издания: 2024
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Номер статьи: 388
DOI: 10.3390/cells13050388
Аннотация: Abstract: The development of resistance to chemotherapy is one of the main problems for effectivecancer treatment. Drug resistance may result from disturbances in two important physiologicalprocesses—cell proliferation and cell death. Importantly, both processes characterize alterations incell metabolism, the level of which is often measured using MTT/MTS assays. To examine resistanceto chemotherapy, different cancer cell lines are usually used for the in vitro modulation of developingresistance. However, after the creation of resistant cell lines, researchers often have difficulty instarting investigations of the mechanisms of insensitivity. In the first stage, researchers shouldaddress the question of whether the drug resistance results from a depression of cell proliferationor an inhibition of cell death. To simplify the choice of research strategy, we have suggested acombination of different approaches which reveal the actual mechanism. This combination includesrapid and high-throughput methods such as the MTS test, the LIVE/DEAD assay, real-time cellmetabolic analysis, and Western blotting. To create chemoresistant tumor cells, we used four differentcancer cell lines of various origins and utilized the most clinically relevant pulse-selection approach.Applying a set of methodological approaches, we demonstrated that three of them were more capableof modulating proliferation to avoid the cytostatic effects of anti-cancer drugs. At the same time, oneof the studied cell lines developed resistance to cell death, overcoming the cytotoxic action.
Добавил в систему: Первушин Николай Викторович

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