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 metalloproteinase8(ADAM8) expression. The ability of propofol to impact the proliferation, migration and cell cycle of pancreatic cancer cell lines was assessed invitro. This was mechanistically explored following the identification of SP1 binding sites within ADAM8, which enabled the regulatory effects of specificity protein1(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.

Highlights

  • In 2018 the pancreatic cancer diagnoses worldwide and 432,000 deaths resulting from pancreatic cancer [1]

  • The ability of propofol to impact the proliferation, migration and cell cycle of a pancreatic cancer cell line was assessed in vitro. This was mechanistically explored following the identification of Specificity protein 1 (SP1) binding sites within ADAM8, which enabled the regulatory effects of SP1 on ADAM8 following propofol treatment to be further explored

  • 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

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Summary

Introduction

In 2018 the pancreatic cancer diagnoses worldwide and 432,000 deaths resulting from pancreatic cancer [1]. A meta-analysis has shown that propofol-based total intravenous anesthesia (TIVA) can observably improve recurrence-free survival rate (pooled HR, 0.78; 95% CI, 0.65 to 0.94; P < 0.01) and overall survival rate (pooled HR, 0.76; 95% CI, 0.63 to 0.92; P < 0.01) for various cancers [5], suggesting that propofol may be involved in tumor suppression. This study aims to address some of the mechanisms associated with this phenomenon. 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

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