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

Abstract

BackgroundInterleukin-8 (IL-8) expression is associated with metastasis in a variety of cancer cells. PurposeHere, 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. MethodsThe 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. ResultsClinically, 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. ConclusionHere, we demonstrate that BBR may be a promising drug to suppress cell invasiveness and growth of TNBC through IL-8-related mechanisms.