Antitumor effects of etodolac, a selective cyclooxygenase-II inhibitor, against human prostate cancer cell lines in vitro and in vivo.
OBJECTIVE
To investigate the effects of the selective cyclooxygenase-2 (COX-2) inhibitor etodolac on prostate cancer cell lines in vitro and in vivo and on E-cadherin expression in prostate cancer cells.


METHODS
We evaluated the cytotoxicity of etodolac on the three prostate cancer cell lines LNCaP, C4-2, and PC-3. We also performed quantitative real-time polymerase chain reaction to measure the mRNA expression of COX-2, Bcl-2, and E-cadherin in these cell lines after etodolac treatment. In addition, we investigated the in vivo antitumor effects of etodolac on a human prostate cancer xenograft model.


RESULTS
Etodolac exhibited significant antitumor effect in vivo and in vitro. The cytotoxicity of etodolac in LNCaP and C4-2 was markedly increased at a dose of 1000 nM in a time-dependent and dose-dependent manner. In the in vivo tumor growth study, the etodolac-treated mice exhibited more significant cytotoxicity than the phosphate-buffered saline-treated mice. Expression of E-cadherin after etodolac treatment tended to increase and that of Bcl-2 to decrease, but the expression of COX-2 had no definite tendency.


CONCLUSIONS
The COX-2 inhibitor etodolac exhibited an antitumor effect on prostate cancer cell lines in vitro and in vivo, and it might be useful for the treatment of hormone-resistant prostate cancer.
Shigemura
Katsumi
K
Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Shirakawa
Toshiro
T
Wada
Yoshitaka
Y
Kamidono
Sadao
S
Fujisawa
Masato
M
Gotoh
Akinobu
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D017308:Etodolac / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D017308:Etodolac