Abstract
Results obtained showed that infection with HCMV prevented the death of THP-1 cells treated with DOX in both active and latent forms of infection. In the presence of mTOR inhibitors (rapamycin and Torin2), the sensitivity of the infected cells to DOX was restored. Rapamycin inhibited the expression of the HCMV protein IE1-p72 and increased sensitivity to DOX. Molecular targets for the creation of new drugs for the treatment of leukemia in patients infected with HCMV were determined.
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REFERENCES
Nikolaou, M., Pavlopoulou, A., Georgakilas, A.G., and Kyrodimos, E., The challenge of drug resistance in cancer treatment: a current overview, Clin. Exp. Metastasis, 2018, vol. 35, no. 4, pp. 309–318. https://doi.org/10.1007/s10585-018-9903-0
Herbein, G., The human cytomegalovirus, from oncomodulation to oncogenesis, Viruses, 2018, vol. 10, no. 8, p. e408. https://doi.org/10.3390/v10080408
Fedorova, N.E., Chernoryzh, Y.Y., Vinogradskaya, G.R., et al., Inhibitor of polyamine catabolism MDL72.527 restores the sensitivity to doxorubicin of monocytic leukemia Thp-1 cells infected with human cytomegalovirus, Biochimie, 2019, vol. 158, pp. 82–89. https://doi.org/10.1016/j.biochi.2018.12.012
Kudchodkar, S.B., Yu, Y., Maguire, T.G., and Al-wine, J.C., Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes, Proc. Natl. Acad. Sci. U.S.A., 2006, vol. 103, no. 38, pp. 14 182–14 187. https://doi.org/10.1073/pnas.0605825103
Cheng, S., Caviness, K., Buehler, J., et al., Transcriptome-wide characterization of human cytomegalovirus in natural infection and experimental latency, Proc. Natl. Acad. Sci. U. S. A., 2017, vol. 114, no. 49, pp. E10586–E10595. https://doi.org/10.1073/pnas.1710522114
Mocarski, E., Shenk, T., Griffiths, P.D., and Pass, F.R., Cytomegaloviruses, in Fields Virology, Knipe, D.M. and Howley, P.M., Eds., 6th ed., Philadelphia, USA: Lippincott Williams and Wilkins, 2013, vol. 2, pp. 1960–2014.
Spector, D.H., Human cytomegalovirus riding the cell cycle, Med. Microbiol. Immunol., 2015, vol. 204, no. 3, pp. 409–419. https://doi.org/10.1007/s00430-015-0396-z
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The work was supported by the Russian Foundation for Basic Research (project nos. 17-04-00812 and 19-04-01218).
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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.
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Translated by M. Batrukova
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Chernoryzh, Y.Y., Fedorova, N.E., Yurlov, K.I. et al. Resistance of THP-1 Leukemia Cells Infected with Cytomegalovirus to Anti-tumor Antibiotic Doxorubicin and Restoration of the Sensitivity by Inhibitors of the PI3K/AKT/mTOR Molecular Pathway. Dokl Biochem Biophys 489, 388–391 (2019). https://doi.org/10.1134/S1607672919060073
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DOI: https://doi.org/10.1134/S1607672919060073