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七氟醚通过 Wnt/β-catenin 信号通路抑制胆管癌。

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

机构信息

Department of Anesthesiology, People's Hospital of Dongxihu District, Wuhan, 430040, China.

People's Hospital of Dongxihu District, No. 81 Huanshan Road, Wujiashan, Dongxihu District, Wuhan, 430040, China.

出版信息

BMC Gastroenterol. 2023 Aug 11;23(1):279. doi: 10.1186/s12876-023-02911-3.

DOI:10.1186/s12876-023-02911-3
PMID:37568083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10422733/
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.

摘要

背景

胆管癌（CCA）是一种源自胆管上皮细胞的难治性恶性肿瘤。本研究旨在探讨七氟醚在 CCA 中的作用及分子机制。

方法

采用 CCK-8 法检测胆管癌细胞增殖，流式细胞术检测胆管癌细胞凋亡。Transwell 检测七氟醚对 TFK1 和 QBC939 细胞迁移和侵袭的影响。Western blot 和 RT-qPCR 检测凋亡相关蛋白和基因的表达，以及 Wnt/β-catenin 信号通路的基因表达。

结果

本研究发现，七氟醚呈剂量依赖性抑制胆管癌细胞增殖。此外，七氟醚诱导胆管癌细胞凋亡，抑制胆管癌细胞迁移和侵袭，以及 Wnt/β-catenin 信号通路，表现为 Wnt3a、β-catenin、c-Myc 和 Cyclin D1 蛋白和 mRNA 表达降低，p-GSK3β 蛋白表达和 p-GSK3β/GSK3β 比值降低。进一步的机制研究表明，Wnt/β-catenin 通路激动剂 SKL2001 逆转了七氟醚对胆管癌细胞的抑制作用。

结论

七氟醚通过抑制 Wnt/β-catenin 信号通路诱导胆管癌细胞凋亡，并抑制其生长、迁移和侵袭。本研究不仅揭示了七氟醚在 CCA 发生发展中的作用，也为 CCA 的治疗提供了新的药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/31073a73e5bd/12876_2023_2911_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/bdf341b7fd17/12876_2023_2911_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/0afaf54e8ef1/12876_2023_2911_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/8136aa9130a9/12876_2023_2911_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/a15e6f9d752b/12876_2023_2911_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/342d83978d36/12876_2023_2911_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/80861f84600d/12876_2023_2911_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/31073a73e5bd/12876_2023_2911_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/bdf341b7fd17/12876_2023_2911_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/0afaf54e8ef1/12876_2023_2911_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/8136aa9130a9/12876_2023_2911_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/a15e6f9d752b/12876_2023_2911_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/342d83978d36/12876_2023_2911_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/80861f84600d/12876_2023_2911_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/724f/10422733/31073a73e5bd/12876_2023_2911_Fig7_HTML.jpg

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