Sevoflurane inhibits cholangiocarcinoma via Wnt/β-catenin signaling pathway. 2023

Hui Cheng, and Qinfang Li
Department of Anesthesiology, People's Hospital of Dongxihu District, Wuhan, 430040, China.

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.

UI MeSH Term Description Entries
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071679 Glycogen Synthase Kinase 3 beta A glycogen synthase kinase-3 type enzyme that functions in ENERGY METABOLISM; EMBRYONIC DEVELOPMENT; and NEUROGENESIS. It is also involved in PROTEIN BIOSYNTHESIS and regulates cell growth and proliferation as a component of the WNT SIGNALING PATHWAY and other signaling pathways. Certain polymorphisms in the GSK3B gene have been associated with PARKINSON DISEASE; ALZHEIMER DISEASE; and BIPOLAR DISORDER. GSK-3beta,GSK3B Protein,GSK3beta,GSK 3beta
D000077149 Sevoflurane A non-explosive inhalation anesthetic used in the induction and maintenance of general anesthesia. It does not cause respiratory irritation and may also prevent PLATELET AGGREGATION. BAX 3084,Fluoromethyl Hexafluoroisopropyl Ether,Fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl Ether,Sevorane,Ultane
D001650 Bile Duct Neoplasms Tumors or cancer of the BILE DUCTS. Bile Duct Cancer,Cancer of Bile Duct,Cancer of the Bile Duct,Neoplasms, Bile Duct,Bile Duct Cancers,Bile Duct Neoplasm,Cancer, Bile Duct,Cancers, Bile Duct,Neoplasm, Bile Duct
D001653 Bile Ducts, Intrahepatic Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct. Bile Duct, Intrahepatic,Duct, Intrahepatic Bile,Ducts, Intrahepatic Bile,Intrahepatic Bile Duct,Intrahepatic Bile Ducts
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051176 beta Catenin A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS. beta-Catenin,Catenin, beta

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