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Article

Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway

  • Authors:
    • Chunli Da
    • Yuting Liu
    • Yiyi Zhan
    • Kai Liu
    • Ruozheng Wang
  • View Affiliations / Copyright

    Affiliations: Department of Intensive Care, Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Anesthesiology, Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Chemotherapy for Lung Cancer, Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Radiotherapy for the Head and Neck, Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China
  • Pages: 2767-2774
    |
    Published online on: March 7, 2016
       https://doi.org/10.3892/or.2016.4661
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Abstract

Epithelial-mesenchymal transition (EMT) is a critical cellular process in cancer metastasis, during which epithelial polarized cells become motile mesenchymal cells. Since transforming growth factor-β (TGF-β) is a potent inducer of EMT, blocking of TGF-β/Smad signaling has become a promising cancer therapy. Nobiletin, a polymethoxy flavonoid from Citrus depressa, has been shown to be valuable for cancer treatment, yet the mechanism remains unclear. In the present study, lung adenocarcinoma A549 and H1299 cells were used to evaluate the effect of nobiletin on EMT induced by TGF-β1. Nobiletin successfully inhibited TGF-β1-induced EMT, migration, invasion and adhesion in vitro, accompanied by attenuation of MMP-2, MMP-9, p-Src, p-FAK, p-paxillin, Snail, Slug, Twist and ZEB1 expression. Nobiletin inhibited the transcriptional activity of Smads without changing the phosphorylation status or translocation of Smads induced by TGF-β1. Moreover, Smad3 is requisite in TGF-β1-stimulated EMT. Smad3 overexpression meaningfully impaired the ability of nobiletin to reverse TGF-β1-induced EMT. In vivo, nobiletin prohibited the growth of metastatic nodules in the lungs of nude mice. Moreover, nobiletin inhibited tumor growth and reversed EMT in mice bearing A549-Luc xenografts, as revealed by IVIS imaging and immunohistochemical analysis. Collectively, the data suggest that nobiletin prevents EMT by inactivating TGF-β1/Smad3 signaling.
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Copy and paste a formatted citation
Spandidos Publications style
Da C, Liu Y, Zhan Y, Liu K and Wang R: Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway. Oncol Rep 35: 2767-2774, 2016.
APA
Da, C., Liu, Y., Zhan, Y., Liu, K., & Wang, R. (2016). Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway. Oncology Reports, 35, 2767-2774. https://doi.org/10.3892/or.2016.4661
MLA
Da, C., Liu, Y., Zhan, Y., Liu, K., Wang, R."Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway". Oncology Reports 35.5 (2016): 2767-2774.
Chicago
Da, C., Liu, Y., Zhan, Y., Liu, K., Wang, R."Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway". Oncology Reports 35, no. 5 (2016): 2767-2774. https://doi.org/10.3892/or.2016.4661
Copy and paste a formatted citation
x
Spandidos Publications style
Da C, Liu Y, Zhan Y, Liu K and Wang R: Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway. Oncol Rep 35: 2767-2774, 2016.
APA
Da, C., Liu, Y., Zhan, Y., Liu, K., & Wang, R. (2016). Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway. Oncology Reports, 35, 2767-2774. https://doi.org/10.3892/or.2016.4661
MLA
Da, C., Liu, Y., Zhan, Y., Liu, K., Wang, R."Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway". Oncology Reports 35.5 (2016): 2767-2774.
Chicago
Da, C., Liu, Y., Zhan, Y., Liu, K., Wang, R."Nobiletin inhibits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway". Oncology Reports 35, no. 5 (2016): 2767-2774. https://doi.org/10.3892/or.2016.4661
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