The inhibitory effects of deep-sea water on doxorubicin‑induced epithelial-mesenchymal transition

Abstract

It has been revealed that the induction of epithelial‑mesenchymal transition (EMT) is associated with drug resistance, leading to tumor recurrence and metastasis. Recent studies have shown that chemotherapeutic agents, besides their therapeutic effects, can induce EMT and enhance invasive and metastatic properties of tumor cells. Previously, we revealed that deep-sea water (DSW) exhibited antimetastatic effects in several human cancer cell lines. In the present study, we investigated the effects of DSW on doxorubicin-induced EMT in MCF-7 human breast cancer cells. When treated with doxorubicin, MCF-7 cells displayed characteristics of EMT, such as, mesenchymal markers (vimentin and fibronectin) and EMT-related transcription factors (Slug and Snail-1) in their RNA expression. However, DSW efficiently inhibited doxorubicin-induced EMT, revealing the decreased expression of vimentin, fibronectin, Slug and Snail-1. Moreover, treatment of MCF-7 cells with DSW significantly suppressed their increased migratory ability by doxorubicin as determined by wound-healing assay. We further demonstrated that the inhibitory effects of DSW on doxorubicin-induced EMT appeared to be mediated by inhibition of the ERK1/2, p38 MAPK and PI3K/AKT signaling pathways. Collectively, our data revealed that DSW has the potential to abolish undesired side-effects of doxorubicin by targeting EMT.