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γ-分泌酶抑制剂通过减少上皮-间质转化来抑制膀胱癌细胞的耐药性和侵袭。

γ-Secretase inhibitor inhibits bladder cancer cell drug resistance and invasion by reducing epithelial-mesenchymal transition.

作者信息

Wang Yibing, Wang Gongxian, Zhang Xiali, Zhou Xiaocheng, Liu Zhihuan, Huang Liang, Liu Rensheng, Lang Bin, Xu Xiaoyuan, Liu Weipeng, Fu Longlong, Fu Bin

机构信息

Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Department of Laboratory Animal Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

出版信息

Mol Med Rep. 2015 Aug;12(2):2821-7. doi: 10.3892/mmr.2015.3750. Epub 2015 May 7.

Abstract

A previous study by our group demonstrated that the expression levels of Notch 1 and Jagged 1 in bladder cancer cells was significantly lower compared with those in normal bladder mucosa, while the expression levels of Notch 1 and Jagged 1 in invasive bladder cancer were higher compared with those in superficial bladder cancer. The present study investigated the effect of the Notch signaling pathway on the drug resistance and invasiveness of bladder cancer cells. It was demonstrated that complete inhibition of the Notch signaling pathway induced significant morphological changes and inhibited cell proliferation and migration (P<0.05). Reverse transcription quantitative polymerase chain reaction and western blot analyses revealed that the mRNA and protein expression levels of E-cadherin were upregulated (P<0.05) and the mRNA and protein expression levels of N-cadherin, vimentin and α-smooth muscle actin were downregulated (P<0.05). The present study concluded that complete inhibition of the Notch signaling pathway inhibited cell proliferation and invasion, and reduced drug resistance in bladder cancer cells, a phenomenon which may be associated with the inhibition of the epithelial-mesenchymal transition.

摘要

我们团队之前的一项研究表明,与正常膀胱黏膜相比,膀胱癌细胞中Notch 1和Jagged 1的表达水平显著降低,而浸润性膀胱癌中Notch 1和Jagged 1的表达水平高于浅表性膀胱癌。本研究探讨了Notch信号通路对膀胱癌细胞耐药性和侵袭性的影响。结果表明,Notch信号通路的完全抑制可诱导显著的形态学变化,并抑制细胞增殖和迁移(P<0.05)。逆转录定量聚合酶链反应和蛋白质印迹分析显示,E-钙黏蛋白的mRNA和蛋白表达水平上调(P<0.05),而N-钙黏蛋白、波形蛋白和α-平滑肌肌动蛋白的mRNA和蛋白表达水平下调(P<0.05)。本研究得出结论,Notch信号通路的完全抑制可抑制膀胱癌细胞的增殖和侵袭,并降低其耐药性,这一现象可能与上皮-间质转化的抑制有关。

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