Sevoflurane inhibits the migration and invasion of glioma cells by upregulating microRNA-637

Int J Mol Med. 2016 Dec;38(6):1857-1863. doi: 10.3892/ijmm.2016.2797. Epub 2016 Nov 8.

Abstract

Cancer cell migration and invasion are essential features of the metastatic process. Volatile anesthetic sevoflurane inhibits the migration and invasion of multiple cancer cell lines; however, its effects on glioma cells are unclear. Emerging evidence suggests that microRNA (miRNA)-637 regulates glioma cell migration and invasion through the Akt1 pathway. Sevoflurane has been shown to modulate a number of miRNAs. In the present study, we examined whether sevoflurane inhibits glioma cell migration and invasion and, if so, whether these beneficial effects are mediated by miRNA-637. U251 glioma cells were treated without (control) or with sevoflurane at low, moderate or high concentrations for 6 h. To explore the molecular mechanisms, an additional group of U251 cells was treated with a miRNA‑637 inhibitor prior to treatment with a high concentration of sevoflurane. Compared with the control group, sevoflurane inhibited the migration and invasion of U251 cells in a dose-dependent manner. Molecular analyses revealed that sevoflurane increased the expression of miRNA‑637 and decreased the expression of Akt1 and phosphorylated Akt1 in a dose-dependent manner. Moreover, the inhibitory effects of sevoflurane on U251 cell migration and invasion were completely abolished by pre-treatment with miRNA‑637 inhibitor, which reversed the sevoflurane-induced reduction in the expression of Akt1 and phosphorylated Akt1 in the U251 cells. These results demonstrate that sevoflurane inhibits glioma cell migration and invasion and that these beneficial effects are mediated by the upregulation of miRNA‑637, which suppresses Akt1 expression and activity. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents for the surgical resection of gliomas to prevent metastases and improve patient outcomes.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioma / genetics*
  • Humans
  • Methyl Ethers / pharmacology*
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Sevoflurane
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • MIRN637 microRNA, human
  • Methyl Ethers
  • MicroRNAs
  • Sevoflurane
  • Proto-Oncogene Proteins c-akt