Open Access

Low-dose paclitaxel modulates tumour fibrosis in gastric cancer

  • Authors:
    • Tomoya Tsukada
    • Sachio Fushida
    • Shinichi Harada
    • Shiroh Terai
    • Yasumichi Yagi
    • Jun Kinoshita
    • Katsunobu Oyama
    • Hidehiro Tajima
    • Itasu Ninomiya
    • Takashi Fujimura
    • Tetsuo Ohta
  • View Affiliations

  • Published online on: January 29, 2013     https://doi.org/10.3892/ijo.2013.1801
  • Pages: 1167-1174
  • Copyright: © Tsukada et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Various treatments have been used for peritoneal dissemination, which is the most common mode of metastasis in gastric cancer, but sufficiently good clinical outcomes have not yet been obtained because of the presence of rich fibrous components and acquired drug resistance. Epithelial-mesenchymal transition (EMT) is one of the major causes of tissue fibrosis and transforming growth factor-β (TGF-β) has a pivotal function in the progression of EMT. Smad proteins play an important role in the TGF-β signalling pathway. The TGF-β/Smad signalling pathway can be modulated by stabilising microtubules with paclitaxel (PTX). Here, we investigated whether paclitaxel can modulate TGF-β/Smad signalling in human peritoneal methothelial cells (HPMCs). To determine the cytostatic concentrations of antineoplastic agents in HPMCs, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl­tetrazolium bromide (MTT) assay was performed using PTX, 5-fluorouracil and cisplatin. The minimum concentration that caused significant inhibition of TGF-β1-induced morphological changes in human peritoneal methothelial cells on pre-treatment with PTX was 5 nM at 48 h (cell viability: 87.1±1.5%, P<0.01). The TGF-β signalling cascade and the status of various fibrous components were evaluated by immunofluorescence staining, real-time quantitative PCR and western blotting. TGF-β signalling induced morphological changes, α-SMA expression and collagen I synthesis in HPMCs and PTX treatment suppressed these EMT-like changes. Moreover, PTX treatment markedly suppressed Smad2 phosphorylation. These data suggest that at a low-dose, PTX can significantly suppress the TGF-β/Smad signalling pathway by inhibiting Smad2 phosphorylation in the human peritoneum and that this can reduce stromal fibrosis.
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April 2013
Volume 42 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Tsukada, T., Fushida, S., Harada, S., Terai, S., Yagi, Y., Kinoshita, J. ... Ohta, T. (2013). Low-dose paclitaxel modulates tumour fibrosis in gastric cancer. International Journal of Oncology, 42, 1167-1174. https://doi.org/10.3892/ijo.2013.1801
MLA
Tsukada, T., Fushida, S., Harada, S., Terai, S., Yagi, Y., Kinoshita, J., Oyama, K., Tajima, H., Ninomiya, I., Fujimura, T., Ohta, T."Low-dose paclitaxel modulates tumour fibrosis in gastric cancer". International Journal of Oncology 42.4 (2013): 1167-1174.
Chicago
Tsukada, T., Fushida, S., Harada, S., Terai, S., Yagi, Y., Kinoshita, J., Oyama, K., Tajima, H., Ninomiya, I., Fujimura, T., Ohta, T."Low-dose paclitaxel modulates tumour fibrosis in gastric cancer". International Journal of Oncology 42, no. 4 (2013): 1167-1174. https://doi.org/10.3892/ijo.2013.1801