Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patientderived organoids.
Int J Oncol
; 57(6): 1307-1318, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33173975
ABSTRACT
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 shortchain 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 threedimensionalcultured 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 transcriptionquantitative 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 radiationinduced cell death and enhanced treatment effects compared with administration of radiation alone. The radiationbutyrate combination reduced the proportion of Ki67 (proliferation marker)positive cells and decreased the number of S phase cells via FOXO3A. Meanwhile, 3/8 CRC organoids were found to be nonresponsive to butyrate with lower expression levels of FOXO3A compared with the responsive cases. Notably, butyrate did not increase radiationinduced 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Retais
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Neoplasias do Colo
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Ácido Butírico
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Quimiorradioterapia Adjuvante
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Proteína Forkhead Box O3
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Oncol
Ano de publicação:
2020
Tipo de documento:
Article