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Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids
Enhancing the radioresponsiveness of colorectal cancer (CRC) is essential for local control and prognosis. However, consequent damage to surrounding healthy cells can lead to treatment failure. We hypothesized that short-chain fatty acids (SCFAs) could act as radiosensitizers for cancer cells, allow...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646587/ https://www.ncbi.nlm.nih.gov/pubmed/33173975 http://dx.doi.org/10.3892/ijo.2020.5132 |
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author | Park, Misun Kwon, Junhye Shin, Hye-Jin Moon, Sun Mi Kim, Sang Bum Shin, Ui Sup Han, Young-Hoon Kim, Younjoo |
author_facet | Park, Misun Kwon, Junhye Shin, Hye-Jin Moon, Sun Mi Kim, Sang Bum Shin, Ui Sup Han, Young-Hoon Kim, Younjoo |
author_sort | Park, Misun |
collection | PubMed |
description | Enhancing the radioresponsiveness of colorectal cancer (CRC) is essential for local control and prognosis. However, consequent damage to surrounding healthy cells can lead to treatment failure. We hypothesized that short-chain fatty acids (SCFAs) could act as radiosensitizers for cancer cells, allowing the administration of a lower and safer dose of radiation. To test this hypothesis, the responses of three-dimensional-cultured organoids, derived from CRC patients, to radiotherapy, as well as the effects of combined radiotherapy with the SCFAs butyrate, propionate and acetate as candidate radiosensitizers, were evaluated via reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and organoid viability assay. Of the three SCFAs tested, only butyrate suppressed the proliferation of the organoids. Moreover, butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone. The radiation-butyrate combination reduced the proportion of Ki-67 (proliferation marker)-positive cells and decreased the number of S phase cells via FOXO3A. Meanwhile, 3/8 CRC organoids were found to be non-responsive to butyrate with lower expression levels of FOXO3A compared with the responsive cases. Notably, butyrate did not increase radiation-induced cell death and improved regeneration capacity after irradiation in normal organoids. These results suggest that butyrate could enhance the efficacy of radiotherapy while protecting the normal mucosa, thus highlighting a potential strategy for minimizing the associated toxicity of radiotherapy. |
format | Online Article Text |
id | pubmed-7646587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-76465872020-11-13 Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids Park, Misun Kwon, Junhye Shin, Hye-Jin Moon, Sun Mi Kim, Sang Bum Shin, Ui Sup Han, Young-Hoon Kim, Younjoo Int J Oncol Articles Enhancing the radioresponsiveness of colorectal cancer (CRC) is essential for local control and prognosis. However, consequent damage to surrounding healthy cells can lead to treatment failure. We hypothesized that short-chain fatty acids (SCFAs) could act as radiosensitizers for cancer cells, allowing the administration of a lower and safer dose of radiation. To test this hypothesis, the responses of three-dimensional-cultured organoids, derived from CRC patients, to radiotherapy, as well as the effects of combined radiotherapy with the SCFAs butyrate, propionate and acetate as candidate radiosensitizers, were evaluated via reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and organoid viability assay. Of the three SCFAs tested, only butyrate suppressed the proliferation of the organoids. Moreover, butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone. The radiation-butyrate combination reduced the proportion of Ki-67 (proliferation marker)-positive cells and decreased the number of S phase cells via FOXO3A. Meanwhile, 3/8 CRC organoids were found to be non-responsive to butyrate with lower expression levels of FOXO3A compared with the responsive cases. Notably, butyrate did not increase radiation-induced cell death and improved regeneration capacity after irradiation in normal organoids. These results suggest that butyrate could enhance the efficacy of radiotherapy while protecting the normal mucosa, thus highlighting a potential strategy for minimizing the associated toxicity of radiotherapy. D.A. Spandidos 2020-10-13 /pmc/articles/PMC7646587/ /pubmed/33173975 http://dx.doi.org/10.3892/ijo.2020.5132 Text en Copyright: © Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Park, Misun Kwon, Junhye Shin, Hye-Jin Moon, Sun Mi Kim, Sang Bum Shin, Ui Sup Han, Young-Hoon Kim, Younjoo Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids |
title | Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids |
title_full | Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids |
title_fullStr | Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids |
title_full_unstemmed | Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids |
title_short | Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids |
title_sort | butyrate enhances the efficacy of radiotherapy via foxo3a in colorectal cancer patient-derived organoids |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646587/ https://www.ncbi.nlm.nih.gov/pubmed/33173975 http://dx.doi.org/10.3892/ijo.2020.5132 |
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