Propofol mediates pancreatic cancer cell activity through the repression of ADAM8 via SP1

Gao,Yutong; Zhou,Yu; Wang,Chunlin; Sample,Klarke M.; Yu,Xiangdi; Ben‑David,Yaacov

doi:10.3892/or.2021.8200

Propofol mediates pancreatic cancer cell activity through the repression of ADAM8 via SP1

Authors:
- Yutong Gao
- Yu Zhou
- Chunlin Wang
- Klarke M. Sample
- Xiangdi Yu
- Yaacov Ben‑David
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Affiliations: Department of Anesthesiology, Guizhou Provincial People's Hospital, The Affiliated Hospital of Guizhou University, Guiyang, Guizhou 550000, P.R. China, Department of Anesthesiology, Zunyi Medical University, Zunyi, Guizhou 563006, P.R. China, State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China, The National Health Commission's Key Laboratory of Immunological Pulmonary Disease, Guizhou Provincial People's Hospital, The Affiliated Hospital of Guizhou University, Guiyang, Guizhou 550000, P.R. China
Published online on: October 6, 2021 https://doi.org/10.3892/or.2021.8200
Article Number: 249

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Abstract

Propofol is a commonly used anesthetic with controversial effects on cancer cells. A growing number of studies have demonstrated that low concentrations of propofol are associated with tumor suppression and when used as an intravenous anesthesia improved recurrence‑free survival rates for many cancers, but deeper insights into its underlying mechanism are needed. The study detailed herein focused upon the effect of propofol on pancreatic cancer cells and the mechanism by which propofol reduces A disintegrin and metalloproteinase 8 (ADAM8) expression. The ability of propofol to impact the proliferation, migration and cell cycle of pancreatic cancer cell lines was assessed in vitro. This was mechanistically explored following the identification of SP1 binding sites within ADAM8, which enabled the regulatory effects of specificity protein 1 (SP1) on ADAM8 following propofol treatment to be further explored. Ultimately, this study was able to show that propofol significantly inhibited the proliferation, migration and invasion of pancreatic cancer cells and decreased the percentage of cells in S‑phase. Propofol treatment was also shown to repress ADAM8 and SP1 expression, but was unable to affect ADAM8 expression following knockdown of SP1. Moreover, a direct physical interaction between SP1 and ADAM8 was verified using co‑immunoprecipitation and dual‑luciferase reporter assays. Cumulatively, these results suggest that propofol represses pathological biological behaviors associated with pancreatic cancer cells through the suppression of SP1, which in turn results in lower ADAM8 mRNA expression and protein levels.

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