Abstract
Taking into account the previously obtained data on the ability of 1-β-D-arabinofuranosylcytosine (AraC) to significantly increase the number of DNA double-strand breaks after cell culture exposure to ionizing radiation in vitro, the aim of this study was to evaluate the combined action of this compound and proton radiation at a focal dose of 10 Gy on of B16 melanoma growth and a number of processes associated with the radiation response of the tumor—in comparison with those after single irradiation with a proton beam in vivo. Significant tumor growth inhibition was established in both groups of irradiated animals in comparison with the control; the most pronounced effect was observed with combined exposure. Molecular cell parameters of cell death and proliferative activity changed approximately to the same extent after the studied exposures compared with the control. However, the proportion of cancer stem cells was reduced by 3.1 times after combined exposure compared with single irradiation (p = 0.003), which, at least in part, explains the greatest inhibition of tumor growth after irradiation in the presence of AraC.
REFERENCES
D. K. Ebner, T. D. Malouff, S. J. Frank, and M. Koto, “The role of particle therapy in adenoid cystic carcinoma and mucosal melanoma of the head and neck,” Int. J. Part. Ther. 8, 273–284 (2021).
“Melanoma of the skin and mucous membranes,” Clinical Guidelines (Russ. Ministry of Health, 2020). https://cr.minzdrav.gov.ru/recomend/546_1. Accessed May 16, 2022.
H. Wang, X. Mu, H. He, and X.-D. Zhang, “Cancer radiosensitizers,” Trends Pharmacol. Sci. 39, 24–48 (2018).
L. Wang, P. Fossati, H. Paganetti, L. Ma, M. Gillison, J. N. Myers, E. Hug, and S. J. Frank, “The biological basis for enhanced effects of proton radiation therapy relative to photon radiation therapy for head and neck squamous cell carcinoma,” Int. J. Part. Ther. 8, 3–13 (2021).
H. Narang, A. Kumar, N. Bhat, B. N. Pandey, and A. Ghosh, “Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer-stem cell trait as biological end points,” Mutat. Res. 780, 35–46 (2015).
L. B. Koricanac, J. J. Zakula, I. M. Petrovic, L. M. Valastro, G. A. Cirrone, G. Cuttone, and A. M. Ristić-Fira, “Anti-tumour activity of fotemustine and protons in combination with bevacizumab,” Chemotherapy 56, 214–222 (2010).
E. A. Krasavin, A. V. Borejko, E. A. Kulikova, T. S. Bulanova, G. N. Timoshenko, and V. N. Chausov, “Method for increasing the frequency of formation of double-strand breaks of DNA in human cells under action of ionizing radiations under conditions of radio modifiers,” RF Invention No. 2699670 (2019).
E. A. Krasavin, A. V. Boreyko, M. G. Zadnepryanetc, E. V. Ilyina, R. A. Kozhina, E. A. Kuzmina, E. A. Kulikova, E. V. Smirnova, G. N. Timoshenko, S. I. Tiounchik, and V. N. Chausov, “Effect of DNA synthesis inhibitors on the biological efficiency of a proton beam in a modified Bragg peak,” Phys. Part. Nucl. Lett. 16, 153–158 (2019).
M. W. Pfaffl, A. Tichopad, C. Prgomet, and T. P. Neuvians, “Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper - Excel-based tool using pair wise correlations,” Biotechnol. Lett. 26, 509–515 (2004).
P. E. Czabotar, Lessene, G. A. Strasser, and J. M. Adams, “Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy,” Nat. Rev. Mol. Cell Biol. 15, 49–63 (2014).
O. N. Matchuk, N. V. Orlova, and I. A. Zamulaeva, “Changes in the relative number of SP cells of melanoma line B16 after radiation exposure in vivo,” Radiats. Biol. Radioekol., No. 5, 487–493 (2016).
V. Dini, M. Belli, and M. A. Tabocchini, “Targeting cancer stem cells: Protons versus photons,” Br. J. Radiol. 92, 20190225 (2019).
L. Vanderwaeren, R. Dok, K. Verstrepen, and S. Nuyts, “Clinical progress in proton radiotherapy: Biological unknowns,” Cancers (Basel) 13, 604 (2021).
X. Zhang, S. H. Lin, B. Fang, M. Gillin, R. Mohan, and J. Y. Chang, “Therapy-resistant cancer stem cells have differing sensitivity to photon versus proton beam radiation,” J. Thorac. Oncol. 8, 1484–1491 (2013).
Alan R. Mitteer, Y. Wang, J. Shah, S. Gordon, M. Fager, P. P. Butter, Jun H. Kim, C. Guardiola-Salmeron, A. Carabe-Fernandez, and Y. Fan, “Proton beam radiation induces DNA damage and cell apoptosis in glioma stem cells through reactive oxygen species,” Sci. Rep. 5, 13961 (2015).
P. Vasefifar, R. M. Azad, L. A. Maleki, S. Najafi, F. Ghrobaninezhad, B. Najafzadeh, H. Alemohammad, M. Amini, A. Baghbanzadeh, and B. Baradaran, “NANOG, as a key cancer stem cell marker in tumor progression,” Gene 827, 146448 (2022).
N. Gawlik-Rzemieniewska and I. Bednarek, “The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells,” Cancer Biol. Ther. 17 (1), 1–10 (2016).
Y.-M. Kim and M. Kahn, “The role of the Wnt signaling pathway in cancer stem cells: Prospects for drug development,” Res. Rep. Biochem. 4, 1–12 (2014).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflicts of interest.
Rights and permissions
About this article
Cite this article
Zamulaeva, I.A., Matchuk, O.N., Selivanova, E.I. et al. Radiobiological Effects of the Combined Action of 1-β-D-Arabinofuranosylcytosine and Proton Radiation on B16 Melanoma in vivo. Phys. Part. Nuclei Lett. 20, 63–75 (2023). https://doi.org/10.1134/S1547477123010107
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1547477123010107