Simvastatin treatment varies the radiation response of human breast cells in 2D or 3D culture
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| Title: | Simvastatin treatment varies the radiation response of human breast cells in 2D or 3D culture |
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| Authors: | Katrin Manda, Dajana Juerß, Paul Fischer, Annemarie Schröder, Annelie Koenen, Guido Hildebrandt |
| Source: | Invest New Drugs |
| Publisher Information: | Springer Science and Business Media LLC, 2020. |
| Publication Year: | 2020 |
| Subject Terms: | Preclinical Studies, Radiation-Sensitizing Agents, Simvastatin, Mitogen-Activated Protein Kinase 3, DNA Repair, Survivin, Cell Culture Techniques, Connective Tissue Growth Factor, Breast Neoplasms, Cell Line, Cell Physiological Phenomena, 3. Good health, Female [MeSH], Histones/metabolism [MeSH], Humans [MeSH], Cell Line [MeSH], Breast Neoplasms/drug therapy [MeSH], Radiation-Sensitizing Agents/pharmacology [MeSH], Cell Physiological Phenomena/drug effects [MeSH], Connective Tissue Growth Factor/metabolism [MeSH], Breast Neoplasms/metabolism [MeSH], Breast Neoplasms/radiotherapy [MeSH], Mitogen-Activated Protein Kinase 3/metabolism [MeSH], Breast/cytology [MeSH], Simvastatin/pharmacology [MeSH], MCF10A, Cell Physiological Phenomena/radiation effects [MeSH], DNA Repair/drug effects [MeSH], Cell Culture Techniques [MeSH], MCF-7, Radiation, DNA Repair/radiation effects [MeSH], 3D, Survivin/metabolism [MeSH], Histones, 03 medical and health sciences, 0302 clinical medicine, Humans, Female, Breast |
| Description: | SummaryBackgroundStatins inhibit the cholesterol biosynthesis and are used as cholesterol-lowering agents in fat-metabolism disorders. Furthermore, several studies state that statins have supportive functions in breast cancer treatment. Therefore, simvastatin (SVA) as a potential radiosensitizer should be investigated on the basis of human breast cells.MethodsFirst, an optimal concentration of SVA for normal (MCF10A) and cancer (MCF-7) cells was identified via growth and cytotoxicity assays that, according to the definition of a radiosensitizer in the narrower sense, enhances the effect of radiation therapy but has no cytotoxic effect. Next, in combination with radiation SVA’s influence on DNA repair capacity and clonogenic survival in 2D and 3D was determined. Furthermore cell cycle distribution, expression of survivin and connective tissue growth factor (CTGF) as well as ERK1 map kinase were analysed.Results1 μM SVA was identified as highest concentration without an influence on cell growth and cytotoxicity and was used for further analyses. In terms of early and residual γH2AX-foci, SVA affected the number of foci in both cell lines with or without irradiation. Different radiation responses were detected in 2D and 3D culture conditions. During the 2D cultivation, a radiosensitizing effect within the clonogenic survival was observable, but not in 3D.ConclusionThe present study suggests that SVA may have potential for radiosensitization. Therefore, it is important to further investigate the role of SVA in relation to the extent of radiosensitization and how it could be used to positively influence the therapy of breast cancer or other entities. |
| Document Type: | Article Other literature type |
| Language: | English |
| ISSN: | 1573-0646 0167-6997 |
| DOI: | 10.1007/s10637-020-01046-6 |
| Access URL: | https://link.springer.com/content/pdf/10.1007/s10637-020-01046-6.pdf https://pubmed.ncbi.nlm.nih.gov/33313978 https://pubmed.ncbi.nlm.nih.gov/33313978/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068713 https://europepmc.org/article/PMC/PMC8068713 https://link.springer.com/article/10.1007/s10637-020-01046-6 https://link.springer.com/article/10.1007/s10637-020-01046-6?error=cookies_not_supported&code=9f3c9f7f-c41c-414a-b07b-4d96bc944ea0 https://link.springer.com/content/pdf/10.1007/s10637-020-01046-6.pdf https://repository.publisso.de/resource/frl:6468398 |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....ff7e1c38bf830ed05c5736275ec9796a |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | SummaryBackgroundStatins inhibit the cholesterol biosynthesis and are used as cholesterol-lowering agents in fat-metabolism disorders. Furthermore, several studies state that statins have supportive functions in breast cancer treatment. Therefore, simvastatin (SVA) as a potential radiosensitizer should be investigated on the basis of human breast cells.MethodsFirst, an optimal concentration of SVA for normal (MCF10A) and cancer (MCF-7) cells was identified via growth and cytotoxicity assays that, according to the definition of a radiosensitizer in the narrower sense, enhances the effect of radiation therapy but has no cytotoxic effect. Next, in combination with radiation SVA’s influence on DNA repair capacity and clonogenic survival in 2D and 3D was determined. Furthermore cell cycle distribution, expression of survivin and connective tissue growth factor (CTGF) as well as ERK1 map kinase were analysed.Results1 μM SVA was identified as highest concentration without an influence on cell growth and cytotoxicity and was used for further analyses. In terms of early and residual γH2AX-foci, SVA affected the number of foci in both cell lines with or without irradiation. Different radiation responses were detected in 2D and 3D culture conditions. During the 2D cultivation, a radiosensitizing effect within the clonogenic survival was observable, but not in 3D.ConclusionThe present study suggests that SVA may have potential for radiosensitization. Therefore, it is important to further investigate the role of SVA in relation to the extent of radiosensitization and how it could be used to positively influence the therapy of breast cancer or other entities. |
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| ISSN: | 15730646 01676997 |
| DOI: | 10.1007/s10637-020-01046-6 |