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Open Access 01-12-2023 | Propofol | Research

Propofol inhibits colon cancer cell stemness and epithelial-mesenchymal transition by regulating SIRT1, Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways

Authors: Runjia Wang, Shuai Li, Qi Hou, Bo Zhang, Huaqing Chu, Yu Hou, Cheng Ni, Li Sun, Yuliang Ran, Hui Zheng

Published in: Discover Oncology | Issue 1/2023

Abstract

Background

Propofol is a common sedative-hypnotic drug used for general anesthesia. Recent studies have drawn attention to the antitumor effects of propofol, but the potential mechanism by which propofol suppresses colon cancer stemness and epithelial-mesenchymal transition (EMT) has not been fully elucidated.

Methods

For the in vitro experiments, we used propofol to treat LOVO and SW480 cells and Cell Counting Kit-8 (CCK-8) to detect proliferation. Self-renewal capacity, cell invasion and migration, flow cytometry analysis, qPCR and Western blotting were performed to detect the suppression of propofol to colon cancer cells and the underlying mechanism. Tumorigenicity and immunohistochemistry experiments were performed to confirm the role of propofol in vivo.

Result

We observed that propofol could suppressed stem cell-like characteristics and EMT-related behaviors, including self-renewal capacity, cell invasion and migration in colon cancer cells, and even suppressed tumorigenicity in vivo. Furthermore, investigations of the underlying mechanism revealed that propofol treatment downregulated SIRT1. SIRT1 overexpression or knockdown affected the stemness and EMT of colon cancer cells. Additionally, propofol reversed stemness and EMT in cells with overexpressing SIRT1 and subsequently inhibited the Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. Wnt/β-catenin pathway inhibitor and PI3K/AKT/mTOR pathway inhibitor blocked the propofol-induced reduction of sphere-formation and cell invasion-migration.

Conclusion

Propofol inhibits LOVO and SW480 cell stemness and EMT by regulating SIRT1 and the Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. Our findings indicate that propofol inhibits SIRT1 in cancer and is advantageous in colon cancer surgical treatment of patients with high SIRT1 expression.

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Title: Propofol inhibits colon cancer cell stemness and epithelial-mesenchymal transition by regulating SIRT1, Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways
Authors: Runjia Wang
Shuai Li
Qi Hou
Bo Zhang
Huaqing Chu
Yu Hou
Cheng Ni
Li Sun
Yuliang Ran
Hui Zheng
Publication date: 01-12-2023
Publisher: Springer US
Keywords: Propofol
Colon Cancer
Colon Cancer
Published in: Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-023-00734-y

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