title: Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator.
abstract: OBJECTIVE
  Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated.
  
  
  METHODS
  Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation.
  
  
  RESULTS
  We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells.
  
  
  CONCLUSIONS
  The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer.
authors.affiliation: Department of Urology, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou, China.
authors.forename: Chongjun
authors.initials: C
authors.lastname: Shi
authors.affiliation: The First Women and Children's Hospital of Huizhou, Huizhou, China.
authors.forename: Nini
authors.initials: N
authors.lastname: Zhang
authors.affiliation: The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Hebei Medical University, Shijiazhuang, China.
authors.forename: Jiewei
authors.initials: J
authors.lastname: Cao
authors.affiliation: Affiliated Hospital of Logistics University of Chinese People's Army Police, Tianjin, China.
authors.forename: Xuyi
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Second Hospital of Hebei Medical University, Shijiazhuang, China.|Hebei Medical University, Shijiazhuang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
mesh_terms: D001241:Aspirin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; C498143:RELA protein, human; C051321:SERPINE1 protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; D014568:Urokinase-Type Plasminogen Activator; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D001241:Aspirin
keywords: Invasion; Matrix metalloproteinase; Nuclear factor-kappa B; Prostate cancer; Urokinase-type plasminogen activator