title: Etodolac, a selective cyclooxygenase-2 inhibitor, induces upregulation of E-cadherin and has antitumor effect on human bladder cancer cells in vitro and in vivo.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) is highly expressed in several human cancers, including bladder cancer. Thus, a selective COX-2 inhibitor could be useful as an antitumor agent for a range of cancers. In the present study, we investigated the antitumor effect and E-cadherin induction of etodolac, a highly selective COX-2 inhibitor, on human bladder cancer cells in vitro and in vivo.
  
  
  METHODS
  We examined the cytotoxicity of etodolac against three human bladder cancer cell lines, T24, 5637, and KK47, and performed quantitative reverse transcriptase-polymerase chain reaction to measure the mRNA expression of COX-2, and E-cadherin.
  
  
  RESULTS
  Etodolac showed significant cytotoxicity only to T24 cells, which expressed the greatest level of COX-2 mRNA and the lowest level of E-cadherin mRNA among the three cell lines. Etodolac also increased the E-cadherin mRNA expression in T24 cells in vitro. We also found that etodolac suppressed tumor growth and induced E-cadherin expression and cell apoptosis in a T24 tumor xenograft mouse model.
  
  
  CONCLUSIONS
  Etodolac exhibited antitumor activity and induced E-cadherin expression in bladder cancer cells and might be useful for the clinical treatment and prevention of bladder cancer, especially in poorly differentiated bladder cancer with high COX-2 and low E-cadherin expression.
authors.affiliation: International Center for Medical Research and Treatment, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Okamoto
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Toshinori
authors.initials: T
authors.lastname: Bito
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shigemura
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hamada
authors.forename: Akinobu
authors.initials: A
authors.lastname: Gotoh
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Masato
authors.initials: M
authors.lastname: Kawabata
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017308:Etodolac / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D015820:Cadherins; D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D017308:Etodolac; D051546:Cyclooxygenase 2