INCREASE OF DRUG RESISTANCE OF ACUTE MYELOID LEUKEMIA CELLS IN MULTICELLULAR AGGREGATES IN VITRO

Autor: S. G. Zakharov, A. K. Golenkov, T. A. Mitina, T. D. Lutskaya, K. A. Belousov, R. S. Fadeev, M. E. Solovieva, A. S. Senotov, V. S. Akatov
Jazyk: ruština
Rok vydání: 2016
Předmět:
Zdroj: Alʹmanah Kliničeskoj Mediciny, Vol 1, Iss 31, Pp 11-16 (2016)
Druh dokumentu: article
ISSN: 2072-0505
2587-9294
DOI: 10.18786/2072-0505-2014-31-11-16
Popis: Background: Therapeutic efficiency in treatment of acute myeloid leukemia (AML) ranges from 20 to 45%. One of the causes of the latter is a drug resistance acquired by leukemic cells under the influence of treatment with antitumor medicines. More important cause is a development of the primary resistance of myeloid leukemic cells to induction of cellular death associated with elemental microenvironment within the bone marrow. Studying primary resistance is very important, and first of all, to prevent development of drug resistance of leukemic cells and, correspondingly, to increase the efficiency of medicamental therapy. Aim: To study the mechanisms of primary resistance of AML cells to induction of cellular death. Materials and methods: Human AML cells of THP-1 line and mononuclear cells of the bone marrow were used in the study of patients with diagnosed AML. Multicellular aggregates were formed during cell cultivating on the 1.5% agarose. To cut off intercellular adhesion, the cells were cultivated in the medium with methylcellulose (0.9%). The viability of the cells was assessed by reduction of Alamar Blue indicator. Results: Within multicellular aggregates, about 75±5% of THP-1 cells were resistant to the activity of recombinant protein izTRAIL, 70±5% – to etoposide, and 40±7% – to sorafenib. Cutting off intercellular contacts decreased the resistance to them. Within multicellular aggregates of primary mononuclear cells, 45±5% of cells were resistant to sorafenib, 57±4% – to etoposide, and all cells were resistant to izTRAIL. Cutting off intracellular adhesion reduced the resistance to sorafenib and etoposide but not to izTRAIL. Conclusion: In multicellular aggregates, AML cells of THP-1 line and mononuclear cells of the bone marrow showed increased resistance to activity of recombinant protein izTRAIL, etoposide, and sorafenib. Diminishing intracellular adhesion in the medium including methylcellulose decreases cellular resistance to cytotoxic agents.
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