Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma

  • Authors:
    • Ryota Kurimoto
    • Takahiro Ebata
    • Shunichiro Iwasawa
    • Tsukasa Ishiwata
    • Yuji Tada
    • Koichiro Tatsumi
    • Yuichi Takiguchi
  • View Affiliations

  • Published online on: May 17, 2017     https://doi.org/10.3892/ol.2017.6188
  • Pages: 944-950
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Abstract

The epithelial-to-mesenchymal transition (EMT) in cancer is associated with invasion, metastasis and chemoresistance. Recent studies have revealed the increased expression of programmed death‑ligand 1 (PD‑L1) in cells undergoing EMT. The underlying mechanism of EMT involves transforming growth factor‑β (TGF‑β) and fibroblast growth factor‑2 (FGF‑2). Pirfenidone and the known EMT‑suppressor nintedanib suppress pulmonary fibrosis partially through suppression of TGF‑β. The present study aimed to determine whether pirfenidone has the potential to induce EMT‑reversion, using nintedanib as a reference. The human lung adenocarcinoma cell lines A‑549, HCC‑827, and PC‑9 were treated with TGF‑β and FGF‑2 to induce EMT. The EMT‑induced cells were further treated with pirfenidone or nintedanib. Phenotypic alterations associated with EMT were assessed by examining the following: i) The expression levels of E‑cadherin, vimentin, fibronectin and slug, using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and fluorescent immunohistochemistry; ii) cell motility via wound‑healing assays; and iii) the expression of PD‑L1 using RT‑qPCR. The combination of TGF‑β and FGF‑2 successfully induced EMT in all three cell lines, characterized by a significant reduction in E‑cadherin expression in the A‑549 and HCC‑827 cells, increased expression levels of vimentin, fibronectin, slug and PD‑L1, and increased cell motility in all three cell lines. Pirfenidone and nintedanib reverted all of these phenotypes, with the exception of unaltered E‑cadherin expression in all three cell lines, and inconsistent expression of vimentin in the HCC‑827 and PC‑9 cells. Thus, pirfenidone and nintedanib have the ability to induce EMT‑reversion in human lung adenocarcinoma.
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July-2017
Volume 14 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Kurimoto R, Ebata T, Iwasawa S, Ishiwata T, Tada Y, Tatsumi K and Takiguchi Y: Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma. Oncol Lett 14: 944-950, 2017.
APA
Kurimoto, R., Ebata, T., Iwasawa, S., Ishiwata, T., Tada, Y., Tatsumi, K., & Takiguchi, Y. (2017). Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma. Oncology Letters, 14, 944-950. https://doi.org/10.3892/ol.2017.6188
MLA
Kurimoto, R., Ebata, T., Iwasawa, S., Ishiwata, T., Tada, Y., Tatsumi, K., Takiguchi, Y."Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma". Oncology Letters 14.1 (2017): 944-950.
Chicago
Kurimoto, R., Ebata, T., Iwasawa, S., Ishiwata, T., Tada, Y., Tatsumi, K., Takiguchi, Y."Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma". Oncology Letters 14, no. 1 (2017): 944-950. https://doi.org/10.3892/ol.2017.6188