Mechanisms of Drug Resistance of Acute Myeloid Leukemia Cells in Three-Dimensional High-Density Cultures: A Study of Intracellular Accumulation of Chemotherapeutic Drugs

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Abstract

Intracellular accumulation of chemotherapeutic drugs in resistant cells of acute myeloid leukemia cultured in a three-dimensional high-density culture was studied. It was shown that neither the dense arrangement of cells, nor the main ABC family transporter proteins most likely affect the increase in drug resistance of acute myeloid leukemia cells in a three-dimensional high-density cell culture. These data indicate the involvement of other mechanisms in increasing drug resistance in three-dimensional high-density cell cultures of acute myeloid leukemia.

About the authors

M. I Kobyakova

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: kobyakovami@gmail.com
Pushchino, Moscow Region, Russia

Y. V Lomovskaya

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Pushchino, Moscow Region, Russia

R. S Fadeev

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Pushchino, Moscow Region, Russia

References

  1. Hoffman R., Cohen H. J., Furie B., and McGlave P. Hematology: Basic principles and practice, 4th ed. (Elsevier/Churchill Livingstone, Philadelphia, 2005).
  2. Marcucci G., Haferlach T., and Döhner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J. Clin. Oncol., 29 (5), 475–486 (2011). doi: 10.1200/JCO.2010.30.2554
  3. Maier S., Dahlstroem C., Haefliger C., Plum A., and Piepenbrock C. Identifying DNA methylation biomarkers of cancer drug response. Am. J. Pharmacogenomics, 5 (4), 223–232 (2005).doi: 10.2165/00129785-200505040-00003
  4. Taylor S. T., Hickman J. A., and Dive C. Epigenetic determinants of resistance to etoposide regulation of Bcl-X(L) and Bax by tumor microenvironmental factors. J. Natl. Cancer Inst., 92 (1), 18–23 (2000).doi: 10.1093/jnci/92.1.18
  5. Захаров С. Г., Голенков А. К., Митина Т. А., Луцкая Т. Д., Белоусов К. А., Фадеев Р. С., Соловьева М. Е., Сенотов А. С. и Акатов В. С. Повышение лекарственной устойчивости клеток острого миелобластного лейкоза в многоклеточных агрегатах in vitro. Альманах клинич. медицины, № 31, 11–16 (2014).
  6. Фадеев Р. С., Соловьева М. Е., Слядовский Д. А., Захаров С. Г., Фадеева И. С., Сенотов А. С., Долгих Н. В., Голенков А. К. и Акатов В. С. Клеточная агрегация повышает лекарственную устойчивость клеток острого миелоидного лейкоза. Биологич. мембраны, 32 (2), 125–134 (2015).
  7. K obyakova M., Lomovskaya Y., Senotov A., Lomovsky A., Minaychev V., Fadeeva I., Shtatnova D., Krasnov K., Zvyagina A., Odinokova I., Akatov V., and Fadeev R. The increase in the drug resistance of acute myeloid leukemia THP-1 cells in high-density cell culture is associated with inflammatory-like activation and antiapoptotic Bcl-2 proteins. Int. J. Mol. Sci., 23 (14), 7881 (2022). doi: 10.3390/ijms23147881
  8. Кобякова М. И., Евстратова Я. В., Сенотов А. С., Ломовский А. И., Минайчев В. В., Звягина А. И., Соловьева М. Е., Фадеева И. С., Акатов В. С. и Фадеев Р. С. Появление признаков дифференцировки и провоспалительного фенотипа у клеток острого миелоидного лейкоза тнр-1 при повышении их trailрезистентности в агрегатах in vitro. Биологич. мембраны, 38 (1), 61–70 (2021).
  9. Grantab R., Sivananthan S., and Tannock I. F. The penetration of anticancer drugs through tumor tissue as a function of cellular adhesion and packing density of tumor cells. Cancer Res., 66 (2), 1033–1039 (2006).doi: 10.1158/0008-5472.CAN-05-3077
  10. Duan C., Yu M., Xu J., Li B. Y., Zhao Y., and Kankala R. K. Overcoming cancer multi-drug resistance (MDR): Reasons, mechanisms, nanotherapeutic solutions, and challenges. Biomed. Pharmacother., 162, 114643 (2023). doi: 10.1016/j.biopha.2023.114643
  11. Choi C.-H. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int., 5, 30 (2005).doi: 10.1186/1475-2867-5-30
  12. Vasconcelos F. C., de Souza P. S., Hancio T., de Faria F. C. C., and Maia R. C. Update on drug transporter proteins in acute myeloid leukemia: Pathological implication and clinical setting. Crit. Rev. Oncol. Hematol., 160, 103281 (2021). doi: 10.1016/j.critrevonc.2021.103281
  13. Gameiro M., Silva R., Rocha-Pereira C., Carmo H., Carvalho F., Bastos M. L., and Remião F. Cellular models and in vitro assays for the screening of modulators of Pgp, MRP1 and BCRP. Molecules, 22 (4), 600.doi: 10.3390/molecules22040600 (2017).

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