Low-dose paclitaxel inhibits the induction of epidermal-mesenchymal transition in the human cholangiocarcinoma CCKS-1 cell line.
Low-dose paclitaxel inhibits the induction of epidermal-mesenchymal transition in the human cholangiocarcinoma CCKS-1 cell line.
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DOI：
10.3892/ol.2013.1494
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发表时间：
2013-10
期刊：
影响因子：
2.9
通讯作者：
Harada S
中科院分区：
文献类型：
--
作者：
Hirose A;Tajima H;Ohta T;Tsukada T;Okamoto K;Nakanuma S;Sakai S;Kinoshita J;Makino I;Furukawa H;Hayashi H;Nakamura K;Oyama K;Inokuchi M;Nakagawara H;Miyashita T;Takamura H;Ninomiya I;Kitagawa H;Fushida S;Fujimura T;Harada S
表皮-间充质转化（EMT）通过提高癌细胞的侵袭能力和转移潜力而赋予癌细胞优势。表皮细胞转变为间充质细胞并因此获得更高的自动化能力的这种现象被认为是癌症发展的关键过程。转化生长因子-β（Transforming growth factor-β，TGF-β）是通过激活蛋白质（包括Smad途径的成员）来加速EMT的重要因子。此外，以前的研究表明，低剂量紫杉醇（PTX）抑制某些细胞系中的EMT，包括癌细胞。本研究确定了低剂量PTX是否能够抑制TGF-β1处理的人胆管癌CCKS-1细胞系中的EMT。首先，PTX对CCKS-1细胞的细胞毒性浓度通过MTT测定和死细胞染色鉴定为约5 nM。因此，对于后续实验，PTX的浓度设定为InM、2.5nM和5 nM。在形态学研究中，CCKS-1细胞变为梭形形态，并通过施用TGF-β1而变得分离。然而，低剂量PTX抑制这些变化，形态学类似于对照细胞在剂量依赖性的方式。同样，免疫荧光和免疫印迹研究显示，CCKS-1细胞表达间充质标志物后，TGF-β1的管理。然而，低剂量PTX抑制间充质标志物的表达，并且CCKS-1细胞表达上皮标志物E-cadherin。特别是，在免疫印迹实验中观察到浓度依赖性效应。这些结果表明，PTX可能能够抑制癌细胞中的EMT，这取决于剂量浓度。
Epidermal-mesenchymal transition (EMT) confers an advantage to cancer cells by improving their invasive capacity and metastatic potential. This phenomenon by which epidermal cells change into mesenchymal cells and therefore acquire a higher ability to automaticity, is considered a key process in cancer development. Transforming growth factor-β (TGF-β) is a significant factor for accelerating EMT through the activation of proteins, including members of the Smad pathway. Furthermore, previous studies have shown that low-dose paclitaxel (PTX) inhibits EMT in certain cell lines, including those of cancer cells. The present study determined whether low-dose PTX was able to inhibit EMT in a human cholangiocarcinoma CCKS-1 cell line that had been treated with TGF-β1. First, the cytotoxic concentration of PTX for the CCKS-1 cells was identified to be ~5 nM by MTT assay and dead cell staining. Therefore, the concentrations of PTX were set as 1 nM, 2.5 nM and 5 nM for the subsequent experiments. In the morphological investigation, the CCKS-1 cells changed into a spindle morphology and became separated by the administration of TGF-β1. However, low-dose PTX inhibited these changes and the morphology resembled the control cells in a dose-dependent manner. Similarly, immunofluorescence and immunoblotting investigations revealed that the CCKS-1 cells expressed mesenchymal markers following the administration of TGF-β1. However, low-dose PTX inhibited the expression of the mesenchymal markers and the CCKS-1 cells expressed the epithelial marker, E-cadherin. In particular, a concentration-dependent effect was observed in the immunoblotting experiments. These results show that PTX may be able to inhibit EMT in cancer cells, depending on the dose concentration.
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悬浮在胶原蛋白凝胶中的上皮可以失去极性，并表达迁移间充质细胞的特征。
影响因子：
7.8
作者：
Greenburg, G;Hay, E D
通讯作者：
Hay, E D
影响因子：
64.8
作者：
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通讯作者：
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影响因子：
8.4
作者：
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通讯作者：
CUNNINGHAM, D
影响因子：
16
作者：
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通讯作者：
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影响因子：
2.7
作者：
Tajima, Hidehiro;Ohta, Tetsuo;Kitamura, Seiko
通讯作者：
Kitamura, Seiko