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

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

  • Discov Oncol. 2023 Jul 25;14(1):137. doi: 10.1007/s12672-023-00734-y.
Runjia Wang 1,  Shuai Li 1,  Qi Hou 1,  Bo Zhang 1,  Huaqing Chu 1,  Yu Hou 1,  Cheng Ni 1,  Li Sun 2,  Yuliang Ran 3,  Hui Zheng 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 2 Department of Anesthesiology, National Cancer Center, National Cancer Clinical Research Center, Shenzhen Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China. lilysun0008@aliyun.com.
  • 3 State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. ran_yuliang@126.com.
  • 4 Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. zhenghui0715@hotmail.com.
PMID: 37490168 DOI: 10.1007/s12672-023-00734-y
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.

Keywords

Colon cancer; Epithelial-mesenchymal transition; Propofol; SIRT1; Stemness.

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