title: Low-dose paclitaxel inhibits the induction of epidermal-mesenchymal transition in the human cholangiocarcinoma CCKS-1 cell line.
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.
authors.affiliation: Department of Gastroenterologic Surgery, Division of Cancer Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirose
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tsukada
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakanuma
authors.forename: Seisho
authors.initials: S
authors.lastname: Sakai
authors.forename: Jun
authors.initials: J
authors.lastname: Kinoshita
authors.forename: Isamu
authors.initials: I
authors.lastname: Makino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.forename: Keishi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inokuchi
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Nakagawara
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamura
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
keywords: cholangiocarcinoma; epidermal-mesenchymal transition; paclitaxel