Sevoflurane inhibits cholangiocarcinoma via Wnt/β-catenin signaling pathway.
Humans
Wnt Signaling Pathway
/ genetics
Sevoflurane
/ pharmacology
beta Catenin
/ metabolism
Glycogen Synthase Kinase 3 beta
/ metabolism
Cell Line, Tumor
Cholangiocarcinoma
/ pathology
Cell Proliferation
/ genetics
Bile Ducts, Intrahepatic
Bile Duct Neoplasms
/ pathology
Cell Movement
Apoptosis
/ genetics
Cholangiocarcinoma
Sevoflurane
Wnt/β-catenin pathway
Journal
BMC gastroenterology
ISSN: 1471-230X
Titre abrégé: BMC Gastroenterol
Pays: England
ID NLM: 100968547
Informations de publication
Date de publication:
11 Aug 2023
11 Aug 2023
Historique:
received:
15
12
2022
accepted:
02
08
2023
medline:
16
8
2023
pubmed:
12
8
2023
entrez:
11
8
2023
Statut:
epublish
Résumé
Cholangiocarcinoma (CCA) is a refractory malignancy derived from bile duct epithelial cells. This study aimed to explore the role and molecular mechanisms of action of sevoflurane in CCA. CCK-8 assay was used to assess the proliferation of cholangiocarcinoma cells, and flow cytometry was used to detect cholangiocarcinoma cell apoptosis. The effects of sevoflurane on TFK1 and QBC939 cell migration and invasion were investigated using a Transwell assay. Western blotting and RT-qPCR were used to assess the expression of apoptosis-related proteins and genes, and gene expression of the Wnt/β-catenin signaling pathway. Our study found that sevoflurane inhibited cholangiocarcinoma cell proliferation in a dose-dependent manner. In addition, sevoflurane induced cholangiocarcinoma cell apoptosis, inhibited cholangiocarcinoma cell migration and invasion, as well as the Wnt/β-catenin signaling pathway evidenced by decreased Wnt3a, β-catenin, c-Myc, and Cyclin D1 protein and mRNA expression, reduced p-GSK3β protein expression and p-GSK3β/GSK3β ratio. Further mechanistic studies revealed that Wnt/β-catenin pathway inducer SKL2001 reversed the inhibitory effect of sevoflurane on cholangiocarcinoma cells. Sevoflurane induces apoptosis and inhibits the growth, migration, and invasion of cholangiocarcinoma cells by inhibiting the Wnt/β-catenin signaling pathway. This study not only revealed the role of sevoflurane in the development of CCA but also elucidated new therapeutic agents for CCA.
Sections du résumé
BACKGROUND
BACKGROUND
Cholangiocarcinoma (CCA) is a refractory malignancy derived from bile duct epithelial cells. This study aimed to explore the role and molecular mechanisms of action of sevoflurane in CCA.
METHODS
METHODS
CCK-8 assay was used to assess the proliferation of cholangiocarcinoma cells, and flow cytometry was used to detect cholangiocarcinoma cell apoptosis. The effects of sevoflurane on TFK1 and QBC939 cell migration and invasion were investigated using a Transwell assay. Western blotting and RT-qPCR were used to assess the expression of apoptosis-related proteins and genes, and gene expression of the Wnt/β-catenin signaling pathway.
RESULTS
RESULTS
Our study found that sevoflurane inhibited cholangiocarcinoma cell proliferation in a dose-dependent manner. In addition, sevoflurane induced cholangiocarcinoma cell apoptosis, inhibited cholangiocarcinoma cell migration and invasion, as well as the Wnt/β-catenin signaling pathway evidenced by decreased Wnt3a, β-catenin, c-Myc, and Cyclin D1 protein and mRNA expression, reduced p-GSK3β protein expression and p-GSK3β/GSK3β ratio. Further mechanistic studies revealed that Wnt/β-catenin pathway inducer SKL2001 reversed the inhibitory effect of sevoflurane on cholangiocarcinoma cells.
CONCLUSIONS
CONCLUSIONS
Sevoflurane induces apoptosis and inhibits the growth, migration, and invasion of cholangiocarcinoma cells by inhibiting the Wnt/β-catenin signaling pathway. This study not only revealed the role of sevoflurane in the development of CCA but also elucidated new therapeutic agents for CCA.
Identifiants
pubmed: 37568083
doi: 10.1186/s12876-023-02911-3
pii: 10.1186/s12876-023-02911-3
pmc: PMC10422733
doi:
Substances chimiques
Sevoflurane
38LVP0K73A
beta Catenin
0
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
279Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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