Blocking C-Raf alleviated high-dose small-volume radiation-induced epithelial mesenchymal transition in mice lung.
Animals
Blotting, Western
Dose-Response Relationship, Radiation
Epithelial-Mesenchymal Transition
/ drug effects
Indoles
/ pharmacology
Lung
/ drug effects
Male
Mice
Mice, Inbred C57BL
Phenols
/ pharmacology
Proto-Oncogene Proteins c-raf
/ antagonists & inhibitors
Radiation Dosage
Radiation Injuries, Experimental
/ drug therapy
Radiosurgery
/ adverse effects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 07 2020
07 07 2020
Historique:
received:
01
11
2019
accepted:
12
06
2020
entrez:
9
7
2020
pubmed:
9
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
The goal of this study was to develop a potential druggable target for lung injury after SABR through the small animal model. Utilising the model, a radiation dose of 70 Gy or 90 Gy was focally (small volume) delivered to the left lung of mice. The highly expressed phosphorylation form of C-Raf was discovered through a protein array experiment, with the protein being extracted from the area of radiated mouse lung tissue, and was confirmed by IHC and western blot. C-Raf activation, along with morphological change and EMT (Epithelial to Mesenchymal Transition) marker expression, was observed after radiation to the mouse type II alveolar cell line MLE-12. C-Raf inhibitor GW5074 was able to reverse the EMT in cells effectively, and was found to be dependent on Twist1 expression. In the animal experiment, pretreatment of GW5074 alleviated EMT and lung injury after 70 Gy radiation was focally delivered to the lung of mice. Conclusively, these results demonstrate that C-Raf inhibitor GW5074 inhibits high-dose small-volume radiation-induced EMT via the C-Raf/Twist1 signalling pathway in mice. Therefore, pharmacological C-Raf inhibitors may be used effectively as inhibitors of SABR-induced lung fibrosis.
Identifiants
pubmed: 32636458
doi: 10.1038/s41598-020-68175-z
pii: 10.1038/s41598-020-68175-z
pmc: PMC7341876
doi:
Substances chimiques
Indoles
0
Phenols
0
Proto-Oncogene Proteins c-raf
EC 2.7.11.1
Raf1 protein, mouse
EC 2.7.11.1
5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone
P0LE4QW0S6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11158Références
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