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Metformin mitigates gastrointestinal radiotoxicity and radiosensitises P53 mutation colorectal tumours via optimising autophagy.
- Source :
-
British Journal of Pharmacology . Sep2020, Vol. 177 Issue 17, p3991-4006. 16p. 2 Diagrams, 6 Graphs. - Publication Year :
- 2020
-
Abstract
- <bold>Background and Purpose: </bold>There is an urgent but unmet need for mitigating radiation-induced intestinal toxicity while radio sensitising tumours for abdominal radiotherapy. We aimed to investigate the effects of metformin on radiation-induced intestinal toxicity and radiosensitivity of colorectal tumours.<bold>Experimental Approach: </bold>Acute and chronic histological injuries of the intestine from mice were used to assess radioprotection and IEC-6 cell line was used to investigate the mechanisms in vitro. The fractionated abdominal radiation model of HCT116 and HT29 tumour grafts was used to determine the effects on colorectal cancer.<bold>Key Results: </bold>Metformin alleviated radiation-induced acute and chronic intestinal toxicity by optimising mitophagy which was AMPK-dependent. In addition, our data indicated that metformin increased the radiosensitivity of colorectal tumours with P53 mutation both in vitro and in vivo.<bold>Conclusion and Implications: </bold>Metformin may be a radiotherapy adjuvant agent for colorectal cancers especially those carrying P53 mutation. Our findings provide a new strategy for further precise clinical trials for metformin on radiotherapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 177
- Issue :
- 17
- Database :
- Academic Search Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 145204217
- Full Text :
- https://doi.org/10.1111/bph.15149