title: Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer.
abstract: BACKGROUND
  Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays an important role in cancer tumorigenesis and progression. We investigated the role of the GSK-3β inhibitor AZD1080 in ovarian cancer cell lines.
  
  
  METHODS
  A2780 and OVCAR3 ovarian cancer cell lines were exposed to AZD1080, after which cell proliferation, cell cycle, invasion, and migration assays were performed. Phalloidin staining was used to observe lamellipodia formation. Reverse transcription polymerase chain reaction and Western blot were used to assess the respective mRNA and protein expression levels of GSK-3β, CDK2, CDK1, cyclin D1, matrix metalloproteinase-9 (MMP9), and Bcl-xL.
  
  
  RESULTS
  AZD1080 exposure suppressed ovarian cancer cell proliferation, invasion, migration, and lamellipodia formation, and induced G1 arrest, which was concentration dependent. AZD1080 also significantly downregulated GSK-3β, CDK2, CDK1, cyclin D1, MMP9, and Bcl-xL expression at both mRNA and protein levels.
  
  
  CONCLUSIONS
  Taken together, our results demonstrate that the GSK-3β inhibitor AZD1080 suppresses ovarian cancer development and therefore may indicate a new direction for ovarian cancer treatment.
authors.affiliation: Department of Gynecology, The First affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gynecology, The First affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Kai-Xuan
authors.initials: KX
authors.lastname: Sun
authors.affiliation: Department of Gynecology, The First affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Miao-Xiao
authors.initials: MX
authors.lastname: Feng
authors.affiliation: Department of Gynecology, The First affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Xiu-Bo
authors.initials: XB
authors.lastname: Sang
authors.affiliation: Department of Gynecology, The First affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Bo-Liang
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Gynecology, The First affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C581774:2-hydroxy-3-(5-((morpholin-4-yl)methyl)pyridin-2-yl)-1H-indole-5-carbonitrile; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D000071679:Glycogen Synthase Kinase 3 beta
keywords: AZD1080; GSK-3β inhibitor; ovarian cancer; progression; tumorigenesis