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The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.
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Medical Radiology and Radiation Safety. 2024. Vol. 69. № 4
DOI:10.33266/1024-6177-2024-69-4-20-24
D.V. Molodtsova, N.Yu. Vorobyeva, L.I. Yashkina, T.M. Trubchenkova, D.V. Guryev, A.N. Osipov
Increased Radioresistance of Human Non-Small Cell Lung
Cancer Cells Surviving Cisplatin Exposure
A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia
Contact person: D.V. Molodtsova, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: To evaluate radioresistance of human non-small cell lung cancer (NSCLC) cells that survived and showed sustained growth after exposure to cisplatin.
Material and methods: The work used the NSCLC cell line A549, which was exposed to cisplatin at a concentration of 2.5 μg/ml four times to obtain a cell population that survives and produces stable growth after exposure to cisplatin, A549Pt. Cell irradiation was carried out on a RUB RUST-M1 X-ray biological installation (Russia) at a dose rate of 0.85 Gy/min. Cell death was assessed using flow cytometry. To analyze the effectiveness of DNA repair from double-strand breaks (DSBs), we used a quantitative assessment of the foci of DNA DSB marker proteins γH2AX and 53BP1.
Results: A549Pt NSCLC cells that survived and grew robustly after exposure to cisplatin exhibited reduced activation of apoptosis and produced less 53BP1 in response to additional cisplatin exposure compared to parental A549 cells. A549Pt also exhibit resistance to X-ray radiation, manifested in a decrease in the quantitative yield of foci of DNA DSB marker proteins γH2AX and 53BP1. The resistance of A549Pt cells to the effects of ionizing radiation, revealed in this work, can significantly reduce the effectiveness of neoadjuvant chemoradiation therapy for malignant neoplasms. Further research is needed to identify the detailed cellular and molecular mechanisms of the resistance of surviving cells to radiation therapy acquired during chemotherapy. In the future, this will increase the effectiveness of treatment of malignant neoplasms and avoid relapses.
Keywords: γH2AX, 53BP1, radioresistance, residual foci, DNA double-strand breaks, Х-ray irradiation, сisplatin
For citation: Molodtsova DV, Vorobyeva NYu, Yashkina LI, Trubchenkova TM, Guryev DV, Osipov AN. Increased Radioresistance of Human Non-Small Cell Lung Cancer Cells Surviving Cisplatin Exposure. Medical Radiology and Radiation Safety. 2024;69(4):20–24.
(In Russian). DOI:10.33266/1024-6177-2024-69-4-20-24
References
1. Molodtsova D., Guryev D.V., Osipov A.N. Composition of Conditioned Media from Radioresistant and Chemoresistant Cancer Cells Reveals miRNA and Other Secretory Factors Implicated in the Development of Resistance. International journal of molecular sciences. 2023;24;22. doi: 10.3390/ijms242216498.
2. Alhaddad L., Osipov A.N., Leonov S. The Molecular and Cellular Strategies of Glioblastoma and Non-Small-Cell Lung Cancer Cells Conferring Radioresistance. International journal of Molecular Sciences. 2022;23;21. doi: 10.3390/ijms232113577.
3. Leonov S., Inyang O., Achkasov K., Bogdan E., Kontareva E., Chen Y., et al. Proteomic Markers for Mechanobiological Properties of Metastatic Cancer Cells. International journal of Molecular Sciences. 2023;24;5. doi: 10.3390/ijms24054773.
4. Pustovalova M., Alhaddad L., Blokhina T., Smetanina N., Chigasova A., Chuprov-Netochin R., et al. The CD44high Subpopulation of Multifraction Irradiation-Surviving NSCLC Cells Exhibits Partial EMT-Program Activation and DNA Damage Response Depending on Their p53 Status. International journal of Molecular Sciences. 2021;22;5. doi: 10.3390/ijms22052369.
5. Twentyman P.R., Wright K.A., Rhodes T. Radiation Response of Human Lung Cancer Cells with Inherent and Acquired Resistance to Cisplatin. International Journal of Radiation Oncology, Biology, Physics. 1991;20;2:217-220. doi: 10.1016/0360-3016(91)90093-j.
6. Britten R.A., Peacock J., Warenius H.M. Collateral Resistance to Photon and Neutron Irradiation Is Associated with Acquired Cis-Platinum Resistance in Human Ovarian Tumour Cells. Radiotherapy and Oncology. 1992;23;3:170-5. doi: 10.1016/0167-8140(92)90327-q.
7. Groen H.J.M., Sleijfer S., Meijer C., Kampinga H.H., Konings A.W.T., De Vries E.G.E., et al. Carboplatin- and Cisplatin-Induced Potentiation of Moderate-Dose Radiation Cytotoxicity in Human Lung Cancer Cell Lines. British Journal of Cancer. 1995;726:1406-11. doi: 10.1038/bjc.1995.522.
8. Wilkins D.E., Ng C.E., Raaphorst G.P. Cisplatin and Low Dose Rate Irradiation in Cisplatin Resistant and Sensitive Human Glioma Cells. International Journal of Radiation Oncology, Biology, Physics. 1996;36;1:105-11. doi: 10.1016/s0360-3016(96)00243-x.
9. Raaphorst G.P. Concomitant Low Dose-Rate Irradiation and Cis Platin Treatment in Ovarian Carcinoma Cell Lines Sensitive and Resistant to Cis Platin Treatment. International Journal of Radiation Biology. 2009;69;5:623-631. doi: 10.1080/095530096145634.
10. Leblanc J.M., Raaphorst G.P. Evaluation of Cisplatin Treatment Given Concurrently with Pulsed Irradiation in Cisplatin Sensitive and Resistant Human Ovarian Carcinoma Cell Lines. International Journal of Radiation Biology. 2009;81;6:429-435. doi: 10.1080/09553000500141447.
11. Britten R.A., Warenius H.M., White R., Peacock J. BSO-Induced Reduction of Glutathione Levels Increases the Cellular Radiosensitivity of Drug-Resistant Human Tumor Cells. International Journal of Radiation Oncology, Biology, Physics. 1992;22;4:769-72. doi: 10.1016/0360-3016(92)90521-i.
12. Osipov A., Chigasova A., Yashkina E., Ignatov M., Fedotov Y., Molodtsova D., et al. Residual Foci of DNA Damage Response Proteins in Relation to Cellular Senescence and Autophagy in X-Ray Irradiated Fibroblasts. Cells. 2023;12;8. doi: 10.3390/cells12081209.
13. Vorobyeva N.Y., Babayan N.S., Grigoryan B.A., Sargsyan A.A., Khondkaryan L.G., Apresyan L.S., et al. Increased Yield of Residual Gammah2ax Foci in p53-Deficient Human Lung Carcinoma Cells Exposed to Subpicosecond Beams of Accelerated Electrons. Bull Exp Biol Med. 2022;172;6:756-759. doi: 10.1007/s10517-022-05472-9.
14. Babayan N.S., Guryev D.V., Vorobyeva N.Y., Grigoryan B.A., Tadevosyan G.L., Apresyan L.S., et al. Colony-Forming Ability and Residual Foci of DNA Repair Proteins in Human Lung Fibroblasts Irradiated with Subpicosecond Beams of Accelerated Electrons. Bull Exp Biol Med. 2021;172;1:22-5. doi: 10.1007/s10517-021-05323-z.
15. Rajkumar P. Cisplatin Concentrations in Long and Short Duration Infusion: Implications for the Optimal Time of Radiation Delivery. Journal of Clinical and Diagnostic Research. 2016. doi: 10.7860/jcdr/2016/18181.8126.
16. Alhaddad L., Chuprov-Netochin R., Pustovalova M., Osipov A.N., Leonov S. Polyploid/Multinucleated Giant and Slow-Cycling Cancer Cell Enrichment in Response to X-ray Irradiation of Human Glioblastoma Multiforme Cells Differing in Radioresistance and TP53/PTEN Status. International Journal of Molecular Sciences. 2023;24;2. doi: 10.3390/ijms24021228.
17. Pustovalova M., Blokhina T., Alhaddad L., Chigasova A., Chuprov-Netochin R., Veviorskiy A., et al. CD44+ and CD133+ Non-Small Cell Lung Cancer Cells Exhibit DNA Damage Response Pathways and Dormant Polyploid Giant Cancer Cell Enrichment Relating to Their p53 Status. International Journal of Molecular Sciences. 2022;23;9:4922. doi: 10.3390/ijms23094922.
18. Pustovalova M., Alhaddad L., Smetanina N., Chigasova A., Blokhina T., Chuprov-Netochin R., et al. The p53-53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure. Int J Mol Sci. 2020;21;9. doi: 10.3390/ijms21093342.
19. Fujisawa S., Romin Y., Barlas A., Petrovic L.M., Turkekul M., Fan N., et al. Evaluation of YO-PRO-1 as an Early Marker of Apoptosis Following Radiofrequency Ablation of Colon Cancer Liver Metastases. Cytotechnology. 2014;66;2:259-273. doi: 10.1007/s10616-013-9565-3.
20. Osipov A.N., Pustovalova M., Grekhova A., Eremin P., Vorobyova N., Pulin A., et al. Low Doses of X-Rays Induce Prolonged and ATM-Independent Persistence of γH2AX foci in Human Gingival Mesenchymal Stem Cells. Oncotarget. 2015;6;29:27275-27287. doi: 10.18632/oncotarget.4739.
21. Osipov A., Chigasova A., Yashkina E., Ignatov M., Fedotov Y., Molodtsova D., et al. Residual Foci of DNA Damage Response Proteins in Relation to Cellular Senescence and Autophagy in X-Ray Irradiated Fibroblasts. Cells. 2023;12;8:1209. doi: 10.3390/cells12081209.
22. Raaphorst G.P., Wilkins D.E., Mao J.P., Miao J.C., Ng C.E. Evaluation of Cross-Resistance between Responses to Cisplatin, Hyperthermia, and Radiation in Human Glioma Cells and Eight Clones Selected for Cisplatin Resistance. Radiation Oncology Investigations. 1999;7;3:153-157. doi: 10.1002/(sici)1520-6823(1999)7:3<153::Aid-roi3>3.0.Co;2-t.
23. Rocha C.R.R., Silva M.M., Quinet A., Cabral-Neto J.B., Menck C.F.M. DNA Repair Pathways and Cisplatin Resistance: an Intimate Relationship. Clinics. 2018;73:e478s. doi: 10.6061/clinics/2018/e478s.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The research was carried out with the support of the State Research Assignment cipher «Signal» (registration number in the USISU R&D system: 123011200048-4).
Contribution. Writing: D.V. Molodtsova, A.N. Osipov; Experimental planning: D.V. Molodtsova, N.Yu. Vorobyeva, A.N. Osipov, D.V. Guryev; Experimental work: D.V. Molodtsova, N.Yu. Vorobyeva, L.I. Yashkina, T.M. Blokhina; Vizualization: A.N. Osipov.
Article received: 20.03.2024. Accepted for publication: 25.04.2024.