Medical Radiology and Radiation Safety. 2025. Vol. 70. № 4
DOI:10.33266/1024-6177-2025-70-4-5-9
A.A. Melnikova1, 2, A.A. Afonin1, L.N. Komarova1, V.O. Saburov2
Investigation of the Combined Effect of Protons and the Chemotherapy Drug Doxorubicin on the Expression of BIRC5 (Survivin) Genes and PMAIP1 (Noxa) in MCF-7 Cells
1 National Research Nuclear University MEPhI, Obninsk, Russia
2 A.F. Tsyb Medical Radiological Research Center, Obninsk, Russia
Contact person: A.A. Melnikova, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: Analysis of PMAIP1 and BIRC5 gene expression in breast cancer cells after proton exposure, both as monotherapy and in combination with doxorubicin.
Material and methods: The object of the study was MCF-7 cells. Four study groups were formed: a group exposed to ionizing radiation; a group treated with doxorubicin; a group of combined exposure to ionizing radiation and doxorubicin; and an untreated control group. The cells were irradiated at the Prometheus proton radiation complex at the A.F. Tsyb MRSC, with a scanning proton beam at a dose of 4 Gy (proton energy of 100 MeV) in the center of the distributed Bragg peak. The cells were treated with the chemotherapy drug doxorubicin at a concentration of 0.004 mg/ml 24 hours before irradiation. Total RNA was isolated using an RNA Solo kit and quantified spectrophotometrically (NanoDrop ND-1000). Reverse transcription and amplification were performed simultaneously in real time using the OneTube RT-PCR kit with SYBR Green I as a fluorescent indicator.
Results: The analysis showed that doxorubicin suppresses the expression of BIRC5 (up to 0.02), which is consistent with its known apoptogenic activity. However, the combined effect of doxorubicin and radiation leads to an increase in BIRC5 expression (up to 0.63) and a simultaneous decrease in PMAIP1 expression (up to 0.0003). This indicates the launch of complex compensatory cell survival mechanisms aimed at suppressing apoptosis and enhancing DNA repair under conditions of combined cytotoxic stress. A less pronounced decrease in BIRC5 expression during ionizing radiation monotherapy (up to 0.16) compared with doxorubicin (0.02) is probably due to differences in the nature and kinetics of DNA damage induced by these agents. The data obtained indicate the nonlinear nature of the cellular response to combined exposure and emphasize the difficulty of predicting the effectiveness of combined radiotherapy.
Conclusion: The results demonstrate the antagonistic interaction of doxorubicin and ionizing radiation in the regulation of apoptosis in MCF-7 cells, emphasizing the need for further research to optimize combination cancer therapy.
Keywords: proton therapy, doxorubicin, combined action, Bcl-2 family proteins, MCF-7, BIRC5, PMAIP1
For citation: Melnikova AA, Afonin AA, Komarova LN, Saburov VO. Investigation of the Combined Effect of Protons and the Chemotherapy Drug Doxorubicin on the Expression of BIRC5 (Survivin) Genes and PMAIP1 (Noxa) in MCF-7 Cells . Medical Radiology and Radiation Safety. 2025;70(4):5–9. (In Russian). DOI:10.33266/1024-6177-2025-70-4-5-9
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PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. A.A. Melnikova – conducting experiments, developing a theoretical basis for research; A.A. Afonin – conducting experiments; L.N. Komarova – development of the research concept, scientific supervision; V.O. Saburov – conducting experiments.
Article received: 20.03.2025. Accepted for publication: 25.04.2025.