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Sevoflurane inhibits cholangiocarcinoma via Wnt/β-catenin signaling pathway.


ABSTRACT:

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

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

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

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.

SUBMITTER: Cheng H 

PROVIDER: S-EPMC10422733 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Sevoflurane inhibits cholangiocarcinoma via Wnt/β-catenin signaling pathway.

Cheng Hui H   Li Qinfang Q  

BMC gastroenterology 20230811 1


<h4>Background</h4>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.<h4>Methods</h4>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 bl  ...[more]

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