Medical Radiology and Radiation Safety. 2024. Vol. 69. № 4
DOI:10.33266/1024-6177-2024-69-4-5-12
E.V. Plotnikov1, 2, 3, M.V. Belousov1, 2, A.G. Drozd1, K.S. Brazovsky1,
M.S. Larkina1, 2, E.S. Sukhikh1, A.A. Artamonov4, I.V. Lomov1, V.I. Chernov1, 5
Study of Radiosensitising Properties of Lithium Ascorbate under Neutron Irradiation in Tumour Growth Models
1 National Research Tomsk Polytechnic University, Tomsk, Russia
2 Siberian State Medical University, Tomsk, Russia
3 Mental Health Research Institute of the Tomsk National Research Medical Center, Tomsk, Russia
4 Institute of Biomedical Problems, Moscow, Russia
5 Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia
Contact person: E.V. Plotnikov, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Background: Radiosensitivity of tumour cells is a serious problem in the treatment of oncological diseases, which, along with the dama-
ging effect of irradiation on healthy tissues, significantly limit the possibilities of radiation therapy; therefore, an important task of modern oncopharmacology is the search and study of new radiosensitizing compounds. The main objective of this study was to investigate the radiosensitising effect of lithium ascorbate in vitro and in vivo under neutron radiation exposure.
Material and methods: Evaluation of biological effect in vitro was performed on cell culture of tumour line HCT-116 (human colorectal cancer). To develop a model of tumour growth in vivo, SPF-nude immunodeficient mice (line Nu/j) were used. In vivo xenografts were formed by subcutaneous injection of cell suspension of HCT-116 cell line at a concentration of 2 million cells per 100 µl. The drug was administered to animals before irradiation by intraperitoneal injection in physiological solution at the rate of 2.4 mM/kg of animal weight. Neutron irradiation of cells was performed on cyclotron P-7M, by neutron flux with average energy of 7.5 MeV in the range of absorbed doses of 0.5‒1.5 Gy. Local irradiation of mice tumours was performed once at a dose of 1.5 Gy on a cyclotron with the same flux parameters. Cell viability was assessed by MTT test. Tumour growth parameters were assessed by measuring the sizes of xenografts and calculating the average volume, tumour doubling time and animal life span.
Results: Enhancement of cytotoxic effect with combined application of radiation exposure and lithium ascorbate in vitro and in vivo was shown. A dose-dependent decrease in cancer cell viability was found when lithium ascorbate was used at a concentration of 0.1‒0.3 mM in combination with neutron irradiation. It was shown that the average tumour volume decreased by more than 50 % in comparison with the control, the xenografts growth rate slowed down to 72 %, and the median life expectancy of experimental animals increased by 86 % when lithium ascorbate and neutron irradiation were combined. Mechanisms of radiosensitising effect by induction of oxidative stress were proposed.
Conclusion: The use of lithium ascorbate results in a more pronounced therapeutic effect of neutron radiation exposure in cellular and animal models of tumour growth.
Keywords: lithium ascorbate, radiosensitization, tumor growth models, colorectal cancer, HCT-116 cells, neutron, cytotoxicity, apoptosis
For citation: Plotnikov EV, Belousov MV, Drozd AG, Brazovsky KS, Larkina MS, Sukhikh ES, Artamonov AA, Lomov IV, Cher-
nov VI.Study of Radiosensitising Properties of Lithium Ascorbate under Neutron Irradiation in Tumour Growth Models. Medical Radiology and Radiation Safety. 2024;69(4):5–12. (In Russian). DOI:10.33266/1024-6177-2024-69-4-5-12
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PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study was carried out within the framework of the Priority 2030 project.
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.03.2024. Accepted for publication: 25.04.2024.