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Adhim, Z,Matsuoka, T,Bito, T,Shigemura, K,Lee, K-M,Kawabata, M,Fujisawa, M,Nibu, K,Shirakawa, T Nature Publishing Group 2011 The British journal of cancer Vol.105 No.3
<P><B>Background:</B></P><P>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.</P><P><B>Methods:</B></P><P>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 <I>in vivo</I> study.</P><P><B>Results:</B></P><P>Within the clinical drug concentrations, only etodolac showed the <I>in vitro</I> growth inhibition in T24 not in the other cell lines. Etodolac reduced <I>SNAIL</I> mRNA and vimentin cell surface expression, and induced <I>E-cadherin</I> mRNA and E-cadherin cell surface expression, in T24. Etodolac also most strongly inhibited the cell migration of T24 <I>in vitro</I> and showed the highest tumour growth inhibition in T24 tumour <I>in vivo</I>.</P><P><B>Conclusion:</B></P><P>Etodolac at clinical doses exhibited induced <I>in vitro</I> and <I>in vivo</I> 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.</P>