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.

Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma

“…We further explored the possible mechanism by which FOXP1 inhibits ICC cell progression. Since the Wnt/β-catenin signaling pathway was previously reported as a vital regulatory factor in cholangiocarcinoma [24][25][26], the key pathway-related proteins, including Wnt3a, phosphorylated GSK3β, and β-catenin, were detected in HCCC-9810 cells after FOXP1 overexpression or knockdown. Unfortunately, the Wnt/β-catenin signaling pathway was not significantly altered by FOXP1 interference (Fig.…”

Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)

“…Furthermore, CCA cells express certain Wnt ligands, including Wnt3, Wnt5a, and Wnt7b, which have the capability to recruit and activate TAMs. Subsequently, TAMs release Wnt, which in turn stimulates the Wnt/β-catenin pathway, leading to increased tumor cell proliferation ( 50 , 51 ). Moreover, in vitro experiments involving the inhibition of Wnt signaling using a Wnt inhibitor have revealed a significant reduction in CCA proliferation and an increase in apoptosis.…”