title: EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer.
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs inhibit the activity of cyclooxygenases (COXs), and their usage reduces the risks associated with prostate cancer. Celecoxib is a selective COX-2 inhibitor and reported to prevent the progression of prostate cancer. However, the mechanisms involved remain unclear. In this study, we investigated the suppression of prostate cancer growth by celecoxib and elucidated the biological relevance of the inhibited pathway in prostate cancer cell lines.
  
  
  METHODS
  Western blotting, quantitative real-time PCR and cell proliferation assay were used to resolve the mechanism of celecoxib in prostate cancer cell line PC3, LNCaP and their derivatives.
  
  
  RESULTS
  Celecoxib induced apoptosis and downregulated EP2, CREB and androgen receptor (AR). Moreover, EP2 antagonist downregulated CREB as well as COX-2 and AR, resulting in the suppression of cell proliferation. Furthermore, EP2 and CREB knockdown induced AR downregulation, indicating that AR suppression by celecoxib is mediated by EP2/CREB signaling.
  
  
  CONCLUSIONS
  Celecoxib exerts antitumor activity through EP2 signaling regulating AR and COX-2 expression. Furthermore, in addition to celecoxib, therapeutics targeting EP2 may also be promising against prostate cancers.
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: E
authors: E
authors: Kashiwagi
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: M
authors: M
authors: Shiota
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: A
authors: A
authors: Yokomizo
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: J
authors: J
authors: Inokuchi
authors: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: T
authors: T
authors: Uchiumi
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: S
authors: S
authors: Naito
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008954:Models, Biological; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000235:genetics; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D052246:Cyclooxygenase 2 Inhibitors; C545644:PTGER2 protein, human; D011720:Pyrazoles; D011944:Receptors, Androgen; D011982:Receptors, Prostaglandin; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013449:Sulfonamides; D000068579:Celecoxib