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

Hirose,Atsushi; Tajima,Hidehiro; Ohta,Tetsuo; Tsukada,Tomoya; Okamoto,Koichi; Nakanuma,Shinichi; Sakai,Seisho; Kinoshita,Jun; Makino,Isamu; Furukawa,Hiroyuki; Hayashi,Hironori; Nakamura,Keishi; Oyama,Katsunobu; Inokuchi,Masafumi; Nakagawara,Hisatoshi; Miyashita,Tomoharu; Takamura,Hiroyuki; Ninomiya,Itasu; Kitagawa,Hirohisa; Fushida,Sachio; Fujimura,Takashi; Harada,Shinichi

doi:10.3892/ol.2013.1494

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

Authors:
- 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
- Takashi Fujimura
- Shinichi Harada
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Affiliations: Department of Gastroenterologic Surgery, Division of Cancer Medicine, Kanazawa University, Kanazawa, Ishikawa 920‑8640, Japan, Center for Biomedical Reserch, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920‑8640, Japan
Published online on: July 25, 2013 https://doi.org/10.3892/ol.2013.1494
Pages: 915-920

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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.

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