Izvestiya vuzov. Yadernaya Energetika

The peer-reviewed scientific and technology journal. ISSN: 0204-3327

Synergetic Effects of the Combined Action of Carbon Ions and the Chemotherapy Drug Doxorubicin on HeLa Cancer Cells

9/23/2021 2021 - #03 Nuclear medicine and biology

Komarova L.N. Mel’nikova A.A. Baldov D.A.

DOI: https://doi.org/10.26583/npe.2021.3.13

UDC: 621.039:577.3

Proton and carbon beam therapy is currently recognized as the most effective and highly accurate form of radiation therapy for deeply located tumors, including radioresistant ones. This is due to the fact that they have all the advantages of spatial dose distribution and, at the same time, are densely ionizing radiations capable of effectively affecting hypoxic, slow-growing tumors and other neoplasms that are insensitive to traditional types of radiation. It is well known that one of the main methods for treating neoplasms is chemotherapy. The predominant mechanism of action of anti-tumor drugs is the induction of DNA damage with the subsequent impossibility of repair. In our study, we used an anti-tumor antibiotic of the anthracycline series, doxorubicin. The assessment of the potential significance of the synergistic interaction of ionizing radiation with chemical preparations in medical radiology remains an urgent and unresolved problem. It is possible to achieve the maximum effect of the combined action of two agents when they act simultaneously. The phenomenon of synergy can be used to optimize the combined use of radiation and chemotherapy in clinical practice. In this regard, it seems relevant to conduct a study for HeLa cancer cells exposed to ionizing radiation, an antitumor drug, as well as their combination. In the course of the study, results were obtained on the manifestation of the synergistic nature of the agents used, which is of great practical and theoretical importance for understanding the mechanism of the combined effect of ionizing radiation and the chemotherapy drug (doxorubicin). The obtained data can be helpful in optimizing the combined effects in order to achieve maximum synergistic interaction


  1. Trofimova O.P., Tkachev S.I., Yurieva T.V. Past and present of radiation therapy in oncology. Klinicheskaya Onkogematologiya. 2013, no. 4, pp. 355-364 (in Russian).
  2. Bekman I.N. Radiation and Nuclear Medicine: Physical and Chemical Aspects. Textbook. Shchyolkovo. Markotin P.Yu. Publ., 2012, 400 p. (in Russian).
  3. Durante M., Loeffler J.S. Sparged particles in radiation oncology. Nat. Rev. Clin. Oncol. 2010, v. 7, no. 1, pp. 37-43; DOI: https://doi.org/10.1038/nrclinonc.2009.183 .
  4. Sridharan D., Asaithamby A., Bailey S. M., Kostes S. V., Dynan W. S., Kronenberg A., Rithideh K. N., Saha J., Shijders A.M., Werner E. Understanding sapseg development processes after HZE-partial exposure: roles of ROS, DNA damage repair and inflammation. Radiat Res. 2015, no.183(1), pp. 1-26.
  5. Yarmonenko S.P., Vainson A.A. Radiobiology of Humans and Animals. Moscow. Vysshaya Shkola Publ., 2004, 549 p. (in Russian).
  6. Perevedchikova N. I. Guide to Chemotherapy of Tumor Diseases. Moscow. Prakticheskaya Meditsina Publ., 2011, 512 p. (in Russian).
  7. Arola O., Saraste A., Pulkki K. Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res., 2000, 60 p.
  8. Bakina O.V., Swarovskaya N.V., Miller A.A., Lozhkomoev A.S., Avgustinovich A.V., Dobrodeev A.Yu., Spirina L.V., Afanasiev S.G. Synergistic effect of antitumor activity of doxorubicin and bi-component nanostructures based on aluminum oxide. Sibirsky Onkologichesky Zhurnal. 2020, no. 19 (2), pp. 82-89; DOI: https://doi.org/10.21294/1814-4861-2020-19-2-82-89 (in Russian).
  9. Bakaev V.A., Ivanov N.A., Lebedeva Zh.S. Ways to reduce the radiation load on patients with proton therapy of eye diseases. Nauchno-Tekhnicheskie Vedomosti SPbGPU. Fiziko- Matematicheskie Nauki. 2017, v. 10, no. 2, pp. 37-44; DOI: https://doi.org/10.18721/JPM.10204 (in Russian).
  10. Rini F. J., Hall E. J., Marino S. A. The oxygen enhancement ratio as a function of neutron energy with mammalian cells in culture. Radiat. Res.1979, v. 78 (1), pp. 25-37.
  11. Guda K., Natale L., Markowitz S. An improved method for staining cell colonies in clonogenicassays. Cytotechnology. 2007, no. 54, pp. 85-88; DOI: https://doi.org/10.1007/s10616-007-9083-2 .
  12. Petin V.G., Zhurakovskaya G.P., Komarova L.N. Radiobiological Bases of Synergistic Interactions in the Biosphere. Moscow. GEOS Publ., 2012, 219 p. (in Russian).
  13. Petin V.G., Zhurakovskaya G.P., Pantyukhina A.G., Rassokhin A.V. Small doses and problems of synergy of environmental factors. Radiatsionnaya Biologiya. Radioekologiya. 1999, v. 39, no. 1, pp. 113-126 (in Russian).
  14. Petin V.G., Komarov V.P. Quantitative Description of the Modification of Radiosensitivity. Moscow. Energoatomizdat Publ., 1989, 192 p. (in Russian).
  15. Petin V.G., Komarova L.N. The importance of the synergistic interaction of ionizing radiation and other harmful factors to enhance the effects of the Chernobyl accident. Radiatsiya i Risk. 2006, v. 15, no. 1-2, pp. 85-113 (in Russian).
  16. Markov N.V., Golubev A.A., Kancirev A.V., Nasonova E.A., Kadirova E.L. Radiobiological studies on heavy ion beams at ITEF. Meditsinskaya Fizika. 2016, no. 2, pp. 29-33 (in Russian).
  17. Pikalov V.A., Antipov Y.M., Zaichkina S.I., Sorokina S.S., Rozanova O.M., Smirnova E.N., Romanchenko S.P., Dyukina O.R., Beketov E.E., Isaeva E.V., Troshina M.V., Lychagin A.A., Solovev A.N., Koryakin S.N., Ulyanenko S.E. Experimental facility «radiobiological test setup on accelerator U-70» as centers for collective use (CCU). In «RuPAC-2018 Russian Particle Accelerator Conference NRC KI-IHEP Protvino. Contributions to the Proceedings». Protvino, 2018, pp. 253-255.
  18. Koryakina E.V., Potetnya V.I., Troshina M.V., Ephimova M.N., Baykuzina R.M., Koryakin S.N., Lychagin A.A., Pikalov V.A., Ulyanenko S.E. Comparison of the biological efficiency of accelerated carbon ions and heavy recoil nuclei on Chinese Hamster cells. Radiatsiya i Risk. 2019, v. 28, no. 3, pp. 96-106 (in Russian).
  19. Troshina M.V., Koryakina E.V., Potetnya V.I., Koryakin S.N., Pikalov V.A., Lychagin A.A., Solovev A.N. The effect of combined proton and carbon ion irradiation on Chinese Hamster B14-150 cells. In «Eighth International Conference on Radiation in Various Fields of Research. Virtual Conference. Book of Abstracts», 2020, 126 p.
  20. Lipengol’ts A.N., Chochlov V.F., Ijevskiy P.V., Kulakov V.N., Sheyno I.N. Investigation of the effectiveness of irradiation of tumor cell cultures with carbon ions. Sibirsky Onkologichesky Zhurnal. 2009, applic. no. 2, pp. 121-122 (in Russian).
  21. Petin V.G., Zhurakovskaya G.P., Kim J.K. Synergistiс effeсts of different pollutants and equidosimetry. Equidosimetry. Springer. 2005, pp. 207-222.
  22. Petin V.G., Zhurakovskaya G.P., Komarova L.N. Fluence rate as a determinant of synergistic interaction of simultaneous action of UV-light and mild heat in the USSR. J. Photoсhem. Photobiol. B.: Biology. 1997, v. 38, pp. 123-128; DOI: https://doi.org/10.1016/s1011-1344(96)07449-0.
  23. Petin V. G., Dergacheva I. P., Romanenko A. G., Ryabova S. V. A new concept of optimization and forecasting of synergy effects under the combined influence of chemical and physical environmental factors. Rossijsky Khimichesky Zhurnal. 1997, v. 41, no. 3, pp. 96-104 (in Russian).
  24. Ryabova S.V., Petin V.G. Mathematical description of mutation yield under the combined effect of various mutagens. Genetika. 1998, v. 34, no. 8, pp. 1151-1156 (in Russian).
  25. Evstratova E.S., Petin V.G. Biophysical interpretation of the dependence of synergism on the intensity of the agents used. Biofizika. 2018, v. 3, no. 6, pp. 1186-1194; DOI: https://doi.org/10.17709/2409-2231-2 020-7-2-8 (in Russian)

particle therapy carbon ions chemotherapy cervical cancer cells HeLa

Link for citing the article: Komarova L.N., Mel’nikova A.A., Baldov D.A. Synergetic Effects of the Combined Action of Carbon Ions and the Chemotherapy Drug Doxorubicin on HeLa Cancer Cells. Izvestiya vuzov. Yadernaya Energetika. 2021, no. 3, pp. 158-168; DOI: https://doi.org/10.26583/npe.2021.3.13 (in Russian).