title: Isoflurane enhances the malignant potential of glioblastoma stem cells by promoting their viability, mobility in vitro and migratory capacity in vivo.
abstract: BACKGROUND
  Isoflurane is one of the most common general anaesthetics used during surgical procedures, including tumour resection. However, the effects of isoflurane on the viability and migration capacity of cancer cells, specifically in the context of brain cancer cells, remain unclear. Therefore, the aim of this study was to evaluate the influence that isoflurane has on the function of glioblastoma stem cells (GCSs) in regards to cell proliferation, survival and migration.
  
  
  METHODS
  U251-GSCs were exposed to isoflurane at clinically relevant concentrations and incubation times. The effects on proliferation, survival and migration capacities of the cells were evaluated in vitro. The potential risk was assessed in mice by intracranial injection of U251-GSCs pretreated with isoflurane. Furthermore, the average tumour volume and migration distance of U251-GSCs from the tumour centre were calculated.
  
  
  RESULTS
  Exposure of U251-GSCs to 1.2% isoflurane for 6 h resulted in increased proliferation (P<0.05) and decreased apoptosis rate (P<0.05) when compared with the control group. In addition, isoflurane exposure caused increased migration capacity in vitro (P<0.05) and the distance migrated was increased in vivo (P<0.05).
  
  
  CONCLUSIONS
  Clinically relevant concentrations and incubation times of isoflurane could promote the viability and mobility of U251-GSCs, suggesting this general anaesthetic may have detrimental effects in glioblastoma by facilitating its growth and migration.
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dangelmajer
authors.affiliation: Department of Pathology, Division of Neuropathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA Department of Neurosurgery, University Medical Center Düsseldorf, Düsseldorf, Germany.
authors.forename: U D
authors.initials: UD
authors.lastname: Kahlert
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: R
authors.initials: R
authors.lastname: Xie
authors.affiliation: Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: A
authors.initials: A
authors.lastname: Shahveranov
authors.affiliation: Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China dy0711@gmail.com tlei@tjh.tjmu.edu.cn.
authors.forename: D
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China dy0711@gmail.com tlei@tjh.tjmu.edu.cn.
authors.forename: T
authors.initials: T
authors.lastname: Lei
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane
keywords: glioblastoma; isoflurane; proliferation and invasion; stem cells