title: Aquaporin-3 Inhibition Reduces the Growth of NSCLC Cells Induced by Hypoxia.
abstract: OBJECTIVE
  Non-small cell lung cancer (NSCLC) is the leading cause of death worldwide. Although aquaporin-3 (AQP3) is widely distributed in mammalian tissues and over-expressed in NSCLC cells, there are limited studies on the effects of AQP3 knockdown on NSCLC cells under hypoxic conditions.
  
  
  METHODS
  The CCK-8 assay was used to calculate cell viability. Scratch-wound healing and transwell assays were used to detect cell migration and invasion. Apoptotic cells were measured by the TUNEL assay. mRNA expression levels were calculated via quantitative RT-PCR. Relative protein levels were determined by immunoblot assays.
  
  
  RESULTS
  AQP3 knockdown substantially reduced proliferation, migration, and invasion of A549 and NCI-H460 cells under hypoxic conditions. Moreover, AQP3 knockdown clearly induced cell apoptosis. Further analysis identified levels of HIF-1α, VEGF, Raf, phosphor-MEK, and phosphor-ERK, whose activities were significantly attenuated in the AQP3 knockdown group.
  
  
  CONCLUSIONS
  These findings indicate that AQP3 knockdown retards the growth of NSCLC cells partially through inhibiting HIF-1α/VEGF and Raf/MEK/ERK signalling pathways.
authors.affiliation: Department of Pharmacy Intravenous Admixture Service, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Hou
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Song-Ling
authors.initials: SL
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Kuang
mesh_terms: D017209:Apoptosis; D051400:Aquaporin 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D051400:Aquaporin 3; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases