In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines.
In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines.
复制标题
DOI：
10.1038/bjc.2011.262
复制
发表时间：
2011-07-26
影响因子：
8.8
通讯作者：
Shirakawa, T.
中科院分区：
文献类型：
--
作者：
Adhim, Z.;Matsuoka, T.;Bito, T.;Shigemura, K.;Lee, K-M;Kawabata, M.;Fujisawa, M.;Nibu, K.;Shirakawa, T.
虽然环氧合酶-2（考克斯-2）抑制剂在浸润性膀胱癌中的抗肿瘤作用已得到证实，但其作用机制尚不清楚。最近，上皮-间充质转化（EMT）促进肿瘤进展的概念已被提出，EMT的一个关键特征是E-钙粘蛋白的下调。在这项研究中，我们研究了考克斯-2抑制剂对膀胱癌细胞逆转EMT和肿瘤生长抑制的作用。本研究采用三种考克斯-2抑制剂依托度酸、塞来昔布和NS-398以及三种人膀胱癌细胞系T24、5637和KK 47。在体内研究中使用T24异种移植肿瘤小鼠模型。在临床药物浓度范围内，只有依托度酸在T24中显示出体外生长抑制作用，而在其他细胞系中没有。依托度酸减少SNAIL mRNA和波形蛋白细胞表面表达，诱导E-cadherin mRNA和E-cadherin细胞表面表达，在T24。依托度酸还在体外最强烈地抑制T24的细胞迁移，并且在体内显示出对T24肿瘤的最高肿瘤生长抑制。依托度酸在临床剂量下表现出诱导的体外和体内抗肿瘤作用和逆转T24细胞EMT的作用。这些结果表明，依托度酸是一个很好的候选人的抗肿瘤或化学预防试剂的高级别膀胱癌。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
56.9
作者：
Raftopoulou, M;Etienne-Manneville, S;Hall, A
通讯作者：
Hall, A
影响因子：
11.2
作者：
Onder, Tamer T.;Gupta, Piyush B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
11.2
作者：
Chaffer, Christine L.;Brennan, Janelle P.;Williams, Elizabeth D.
通讯作者：
Williams, Elizabeth D.
影响因子：
4.8
作者：
Mendez, Melissa G.;Kojima, Shin-Ichiro;Goldman, Robert D.
通讯作者：
Goldman, Robert D.
影响因子：
4.5
作者：
Kenney, Patrick A.;Wszolek, Matthew F.;Summerhayes, Ian C.
通讯作者：
Summerhayes, Ian C.