In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines

Z. Adhim, T. Matsuoka, T. Bito, K. Shigemura, Kyung-Mi Lee, M. Kawabata, M. Fujisawa, K. Nibu, T. Shirakawa

Research output: Contribution to journalArticle

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Abstract

Background: Although the anti-tumour effect of cyclooxygenase-2 (Cox-2) inhibitors in invasive bladder cancer has been confirmed, its mechanisms of action are unclear. Recently, the concept of an epithelial-to-mesenchymal transition (EMT) promoting carcinoma progression has been suggested, and a key feature of the EMT is the downregulation of E-cadherin. In this study, we investigated the effect of Cox-2 inhibitors on reversal EMT and tumour growth inhibition in bladder cancer cells. Methods: We used three Cox-2 inhibitors, etodolac, celecoxib and NS-398 and three human bladder cancer cell lines, T24, 5637 and KK47, in this study. T24 xenograft tumour mouse model was used in the in vivo study.Results:Within the clinical drug concentrations, only etodolac showed the in vitro growth inhibition in T24 not in the other cell lines. Etodolac reduced SNAIL mRNA and vimentin cell surface expression, and induced E-cadherin mRNA and E-cadherin cell surface expression, in T24. Etodolac also most strongly inhibited the cell migration of T24 in vitro and showed the highest tumour growth inhibition in T24 tumour in vivo. Conclusion: Etodolac at clinical doses exhibited induced in vitro and in vivo anti-tumour effects and reversal effect of EMT in T24. These results suggest that etodolac is a good candidate for an anti-tumour or chemopreventive reagent for high-grade bladder cancer.

Original languageEnglish
Pages (from-to)393-402
Number of pages10
JournalBritish Journal of Cancer
Volume105
Issue number3
DOIs
Publication statusPublished - 2011 Jul 26

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Etodolac
Epithelial-Mesenchymal Transition
Cyclooxygenase 2 Inhibitors
Urinary Bladder Neoplasms
Cell Line
Cadherins
Neoplasms
Celecoxib
Growth
Messenger RNA
Vimentin
In Vitro Techniques
Heterografts
Cell Movement
Down-Regulation
Carcinoma
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines. / Adhim, Z.; Matsuoka, T.; Bito, T.; Shigemura, K.; Lee, Kyung-Mi; Kawabata, M.; Fujisawa, M.; Nibu, K.; Shirakawa, T.

In: British Journal of Cancer, Vol. 105, No. 3, 26.07.2011, p. 393-402.

Research output: Contribution to journalArticle

Adhim, Z. ; Matsuoka, T. ; Bito, T. ; Shigemura, K. ; Lee, Kyung-Mi ; Kawabata, M. ; Fujisawa, M. ; Nibu, K. ; Shirakawa, T. / In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines. In: British Journal of Cancer. 2011 ; Vol. 105, No. 3. pp. 393-402.
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