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.
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.
Okamoto
Asako
A
International Center for Medical Research and Treatment, Kobe University School of Medicine, Kobe, Japan.
Shirakawa
Toshiro
T
Bito
Toshinori
T
Shigemura
Katsumi
K
Hamada
Katsuyuki
K
Gotoh
Akinobu
A
Fujisawa
Masato
M
Kawabata
Masato
M
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*
D015820:Cadherins; D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D017308:Etodolac; D051546:Cyclooxygenase 2