TITLE

Low-dose paclitaxel inhibits the induction of epidermal-mesenchymal transition in the human cholangiocarcinoma CCKS-1 cell line

AUTHOR(S)
ATSUSHI HIROSE; HIDEHIRO TAJIMA; TETSUO OHTA; TOMOYA TSUKADA; KOICHI OKAMOTO; SHINICHI NAKANUMA; SEISHO SAKAI; JUN KINOSHITA; ISAMU MAKINO; HIROYUKI FURUKAWA; HIRONORI HAYASHI; KEISHI NAKAMURA; KATSUNOBU OYAMA; MASAFUMI INOKUCHI; HISATOSHI NAKAGAWARA; TOMOHARU MIYASHITA; HIROYUKI TAKAMURA; ITASU NINOMIYA; HIROHISA KITAGAWA; SACHIO FUSHIDA
PUB. DATE
August 2013
SOURCE
Oncology Letters;2013, Vol. 6 Issue 4, p915
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
110397623

 

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