title: Sevoflurane promotes the expansion of glioma stem cells through activation of hypoxia-inducible factors in vitro.
abstract: BACKGROUND
  Growing evidences indicate that inhalational anaesthetics can enhance the growth and malignant potential of tumour cells and may affect tumour recurrence after surgery. Tumour stem cells play a vital role in tumour recurrence. This study investigates the effect of sevoflurane on glioma stem cells (GSCs) in vitro and the underlying molecular mechanisms in this process.
  
  
  METHODS
  Cultured GSCs were exposed to clinically relevant concentrations and durations of sevoflurane exposure. Cell proliferation and self-renewal capacity were determined. Expression of the stem cell marker CD133, vascular endothelial growth factor (VEGF), hypoxia-inducible factors (HIFs), and phosphorylated Akt, which is a protein kinase invoved in multiple cellular processes, were measured using western blotting. Small interfering RNAs and an Akt inhibitor were used to investigate specific pathways.
  
  
  RESULTS
  Compared with controls, cells exposed to 2% sevoflurane for 6 h induced a larger number of proliferated cells (31.2±7.6% vs 19.0±5.8%; P<0.01). Levels of CD133, VEGF, HIF-1α, HIF-2α, and p-Akt were up-regulated by sevoflurane in a time- and concentration-dependent manner. Small interfering RNA against HIFs decreased the percentage of proliferating GSCs after sevoflurane exposure and pre-treatment of cells with an Akt inhibitor abrogated the expression of HIFs induced by sevoflurane.
  
  
  CONCLUSIONS
  Sevoflurane can promote the expansion of human GSCs through HIFs in vitro. Inhaled anaesthetics may enhance tumour growth through tumour stem cells.
authors.affiliation: Department of Anaesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: S J
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Department of Anaesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anaesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: Q S
authors.initials: QS
authors.lastname: Chen
authors.affiliation: Department of Anaesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: L N
authors.initials: LN
authors.lastname: Yu
authors.affiliation: Department of Anaesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: F J
authors.initials: FJ
authors.lastname: Zhang
authors.affiliation: Department of Anaesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China yanminzju@163.com.
authors.forename: M
authors.initials: M
authors.lastname: Yan
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects*; D066298:In Vitro Techniques; D008738:Methyl Ethers / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000187:drug effects; D000077149:Sevoflurane; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008738:Methyl Ethers; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D000077149:Sevoflurane
keywords: AC133 antigen; glioma; hypoxia-inducible factor-1α; neoplastic stem cells; sevoflurane