Open Access

Narasin inhibits tumor metastasis and growth of ERα‑positive breast cancer cells by inactivation of the TGF‑β/SMAD3 and IL‑6/STAT3 signaling pathways

  • Authors:
    • Jing Chen
    • Xieping Huang
    • Na Li
    • Boxia Liu
    • Zhanbing Ma
    • Jun Ling
    • Wenjun Yang
    • Tao Li
  • View Affiliations

  • Published online on: October 21, 2020     https://doi.org/10.3892/mmr.2020.11624
  • Pages: 5113-5124
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Treatment of human estrogen receptor (ER)‑positive breast cancer (ER+ BC) using conventional chemotherapy remains a challenge and is often ineffective as a result of tumor metastasis. The present study aimed to investigate the ability of narasin, an ionophore antibiotic, to potentially inhibit tumor metastasis and growth in human ER+ BC. Narasin was found to have significant inhibitory abilities on cell proliferation, migration and invasion in ER+ BC cell lines MCF‑7 and T47D compared with the triple‑negative BC cell MDA‑MB‑231. For the in vivo studies, narasin effectively decreased the number of tumor metastasis nodules, tumor volume and weight without apparent toxicity in human MCF‑7 nude mouse left ventricle injection tumor metastasis and xenograft models. Mechanistically, it demonstrated that exposure to TGF‑β or IL‑6 induced the expression of epithelial‑mesenchymal transition (EMT) markers in ER+ BC cell lines. On the contrary, narasin dose‑dependently reversed EMT by increasing the expression of E‑cadherin and decreasing the expression of N‑cadherin, vimentin, β‑catenin and zinc finger E‑box‑binding homeobox 1 at the protein and gene expression levels. Gene microarray, molecular docking and western blotting were performed to demonstrate that those protein and gene expression levels are regulated by the inactivation of the TGF‑β/phosphorylated (p)‑SMAD3 and IL‑6/p‑STAT3 signaling pathways. Taken together, these findings indicated that narasin may be a promising candidate that can be further optimized for the treatment of human ER+ BC.
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December-2020
Volume 22 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Chen J, Huang X, Li N, Liu B, Ma Z, Ling J, Yang W and Li T: Narasin inhibits tumor metastasis and growth of ERα‑positive breast cancer cells by inactivation of the TGF‑β/SMAD3 and IL‑6/STAT3 signaling pathways. Mol Med Rep 22: 5113-5124, 2020
APA
Chen, J., Huang, X., Li, N., Liu, B., Ma, Z., Ling, J. ... Li, T. (2020). Narasin inhibits tumor metastasis and growth of ERα‑positive breast cancer cells by inactivation of the TGF‑β/SMAD3 and IL‑6/STAT3 signaling pathways. Molecular Medicine Reports, 22, 5113-5124. https://doi.org/10.3892/mmr.2020.11624
MLA
Chen, J., Huang, X., Li, N., Liu, B., Ma, Z., Ling, J., Yang, W., Li, T."Narasin inhibits tumor metastasis and growth of ERα‑positive breast cancer cells by inactivation of the TGF‑β/SMAD3 and IL‑6/STAT3 signaling pathways". Molecular Medicine Reports 22.6 (2020): 5113-5124.
Chicago
Chen, J., Huang, X., Li, N., Liu, B., Ma, Z., Ling, J., Yang, W., Li, T."Narasin inhibits tumor metastasis and growth of ERα‑positive breast cancer cells by inactivation of the TGF‑β/SMAD3 and IL‑6/STAT3 signaling pathways". Molecular Medicine Reports 22, no. 6 (2020): 5113-5124. https://doi.org/10.3892/mmr.2020.11624