Propofol suppresses osteosarcoma cell function by regulating FOXO1/TUSC7

J Pharm Pharmacol. 2021 Apr 27;73(6):720-725. doi: 10.1093/jpp/rgab004.

Abstract

Objectives: Accumulated evidence demonstrates that propofol has antitumour roles in various cancers. However, the role of propofol in osteosarcoma is still unclear. Therefore, we aim to determine the role of propofol on osteosarcoma and further explore its potential mechanism.

Methods: Cell proliferation, migration and invasion of osteosarcoma were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing and transwell assay, respectively. The interaction between FoxO1 and TUSC7 was determined using luciferase reporter assay and chromatin immunoprecipitation.

Results: Propofol treatment significantly decreased cell proliferation, migration and invasion in U2OS cells. Propofol promoted TUSC7 expression by enhancing transcriptional factor FOXO1 that leads to inactivation of AKT/GSK3β signalling resulting in the suppression of cell proliferation, migration and invasion.

Conclusions: Propofol suppresses cell proliferation, migration and invasion of osteosarcoma cells through FOXO1/TUSC7 axis by regulating AKT/GSK3β signalling.

Keywords: AKT/GSK3β; FOXO1; LncRNA TUSC7; osteosarcoma; propofol.

MeSH terms

  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Forkhead Box Protein O1 / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Neoplasm Invasiveness / prevention & control
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Propofol / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / metabolism
  • Signal Transduction / drug effects

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • RNA, Long Noncoding
  • loc285194 LncRNA, human
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Propofol