title: Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α.
abstract: OBJECTIVE
  Hypoxia promotes the progression of lung cancer cells. Unfortunately, anesthetic technique might aggravate hypoxia of lung cancer cells. Sevoflurane is a commonly used anesthetic. Its effect on hypoxia-induced aggressiveness of lung cancer cells remains unknown. The aim of the study is to investigate the effects of sevoflurane on hypoxia-induced growth and metastasis of lung cancer cells. As hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in mediating the adaptation and tolerance of cancer cells under hypoxic microenvironment, the role of HIF-1α in the effect of sevoflurane on hypoxia-induced growth and metastasis has also been elucidated.
  
  
  METHODS
  A549 cells were treated with normoxia, hypoxia, co-treatment of sevoflurane and hypoxia, and dimethyloxaloylglycine (DMOG, a HIF-1α agonist) for 4 h, respectively. MTT assay and colony formation assay were used to evaluate cell growth. Transwell assay was performed to detect invasion and migration ability. The protein level of HIF-1α, X-linked inhibitor of apoptosis protein (XIAP), survivin, fascin, heparanase (HPA), and p38 MAPK were determined by Western blotting.
  
  
  RESULTS
  Hypoxia enhanced proliferation and metastatic potential of cells. Sevoflurane could suppress hypoxia-induced growth and metastasis ability of cells. Furthermore, HIF-1α, XIAP, survivin, fascin and HPA were down-regulated significantly by the co-treatment of sevoflurane and hypoxia as compared to hypoxia treatment. DMOG abolished the inhibiting effects of sevoflurane on hypoxia-induced growth and metastasis ability of cells. In addition, sevoflurane partly reversed the increase of p38 MAPK activity that was induced by hypoxia.
  
  
  CONCLUSIONS
  Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes. Moreover, p38 MAPK signaling pathway was involved in the regulation of HIF-1α by sevoflurane.
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China. lhlh2003@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China.
authors.forename: Cheng Xiang
authors.initials: CX
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China.
authors.forename: Han Bing
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China.
authors.forename: Hong Zhen
authors.initials: HZ
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Lai
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China.
authors.forename: Mei Juan
authors.initials: MJ
authors.lastname: Liao
authors.affiliation: Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008738:Methyl Ethers / Q000494:pharmacology*; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008738:Methyl Ethers; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D000077149:Sevoflurane; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Hypoxia-inducible factor-1α; Lung cancer cells; Sevoflurane