Emodin inhibits epithelial‑mesenchymal transition and metastasis of triple negative breast cancer via antagonism of CC‑chemokine ligand 5 secreted from adipocytes

  • Authors:
    • Xiaoyun Song
    • Xiqiu Zhou
    • Yuenong Qin
    • Jianfeng Yang
    • Yu Wang
    • Zhenping Sun
    • Kui Yu
    • Shuai Zhang
    • Sheng Liu
  • View Affiliations

  • Published online on: April 23, 2018     https://doi.org/10.3892/ijmm.2018.3638
  • Pages: 579-588
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Abstract

Triple negative breast cancer (TNBC) has the lowest survival rate of the breast cancer subtypes owing to its aggressive and metastatic behavior. It has been reported that peritumoral adipose tissue contributes to the cell invasiveness and dissemination of TNBC. Emodin is an active anthraquinone derivative isolated from Rheum palmatum, with anticancer properties that have been reported to inhibit lung metastasis in a nude mouse xenograft model. In the present study, the effects of emodin on human TNBC cells and adipocytes were investigated in vivo and in vitro. The TNBC cell lines MDA‑MB‑231 and MDA‑MB‑453 were co‑cultured with human adipocytes and treated with either emodin or epirubicin. Cell proliferation was assessed by MTT assay and migration and invasion were examined using a wound healing assay and a Transwell assay. interleukin‑8, CC‑chemokine ligand 5 (CCL5) and insulin‑like growth factor‑1 levels in the culture supernatants were detected by ELISA. The epithelial‑mesenchymal transition (EMT) or metastasis associated markers were determined by western blot analysis. Nude mice fed with a high fat and sugar diet were used investigate the in vivo effect of emodin. The results showed that emodin inhibited TNBC proliferation and invasion more efficiently than epirubicin when co‑cultured with adipocytes by downregulating the level of CCL5 in adipocyte supernatants; inhibiting the expression level of protein kinase B (AKT); and activating glycogen synthase kinase‑3i (GSK3) and β‑catenin. This led to the suppressed expression of EMT‑ and invasion‑associated markers, including vimentin, snail, matrix metalloproteinase (MMP)‑2 and MMP‑9, and upregulation of E‑cadherin, contributing to the inhibition of invasion. The in vivo assay showed that emodin inhibited tumor growth, and suppressed the lung and liver metastasis of TNBC cells by decreasing the secretion of CCL5 in mice fed a high fat and sugar diet more efficiently when compared with epirubicin. In conclusion, emodin inhibited the secretion of CCL5 from adipocytes, inhibited the EMT of TNBC cells, and inhibited tumor growth and lung and liver metastasis, which indicated a novel role of emodin in preventing the metastasis of TNBC.
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July-2018
Volume 42 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Song X, Zhou X, Qin Y, Yang J, Wang Y, Sun Z, Yu K, Zhang S and Liu S: Emodin inhibits epithelial‑mesenchymal transition and metastasis of triple negative breast cancer via antagonism of CC‑chemokine ligand 5 secreted from adipocytes. Int J Mol Med 42: 579-588, 2018
APA
Song, X., Zhou, X., Qin, Y., Yang, J., Wang, Y., Sun, Z. ... Liu, S. (2018). Emodin inhibits epithelial‑mesenchymal transition and metastasis of triple negative breast cancer via antagonism of CC‑chemokine ligand 5 secreted from adipocytes. International Journal of Molecular Medicine, 42, 579-588. https://doi.org/10.3892/ijmm.2018.3638
MLA
Song, X., Zhou, X., Qin, Y., Yang, J., Wang, Y., Sun, Z., Yu, K., Zhang, S., Liu, S."Emodin inhibits epithelial‑mesenchymal transition and metastasis of triple negative breast cancer via antagonism of CC‑chemokine ligand 5 secreted from adipocytes". International Journal of Molecular Medicine 42.1 (2018): 579-588.
Chicago
Song, X., Zhou, X., Qin, Y., Yang, J., Wang, Y., Sun, Z., Yu, K., Zhang, S., Liu, S."Emodin inhibits epithelial‑mesenchymal transition and metastasis of triple negative breast cancer via antagonism of CC‑chemokine ligand 5 secreted from adipocytes". International Journal of Molecular Medicine 42, no. 1 (2018): 579-588. https://doi.org/10.3892/ijmm.2018.3638