Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells

Phytomedicine. 2018 Nov 15;50:43-49. doi: 10.1016/j.phymed.2018.08.004. Epub 2018 Aug 7.

Abstract

Background: Interleukin-8 (IL-8) expression is associated with metastasis in a variety of cancer cells.

Purpose: Here, we investigated the regulatory mechanism of IL-8 expression as well as the pharmacological effect of berberine (BBR) on IL-8 expression in triple-negative breast cancer (TNBC) cells.

Methods: The clinical value of IL-8 was analyzed by from a public database [Kaplan‑Meier plotter database. IL-8 mRNA and protein expression was analyzed by real-time PCR and ELISA, respectively. Cell invasion was analyzed by Boyden chamber assay. Tumor cell growth was analyzed by colony forming assay.

Results: Clinically, we observed that breast cancer patients with highly expressed IL-8 are associated with poor outcomes in areas such as relapse-free, overall, and distant metastasis-free survival. We showed that IL-8 expression is higher in TNBC cells than in non-TNBC cells. In addition, the rates of cell invasion were significantly increased by IL-8 treatment. These IL-8 levels were decreased by EGFR (Neratinib and Afatinib) and MEK (PD98059) inhibitors in TNBC cells. Finally, we observed that BBR dramatically suppresses IL-8 expression. In addition, BBR also inhibited cell invasiveness and anchorage-independent growth. Interestingly, our results showed that BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation.

Conclusion: Here, we demonstrate that BBR may be a promising drug to suppress cell invasiveness and growth of TNBC through IL-8-related mechanisms.

Keywords: Berberine; Cell invasion; IL-8; MEK/ERK pathway; Triple-negative breast cancer.

MeSH terms

  • Berberine / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Interleukin-8 / metabolism*
  • MAP Kinase Signaling System / drug effects*
  • Neoplasm Recurrence, Local
  • Phosphorylation
  • Triple Negative Breast Neoplasms / metabolism*

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Berberine
  • EGFR protein, human
  • ErbB Receptors