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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...

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Autores principales: Park, Misun, Kwon, Junhye, Shin, Hye-Jin, Moon, Sun Mi, Kim, Sang Bum, Shin, Ui Sup, Han, Young-Hoon, Kim, Younjoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
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.
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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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