Emodin attenuates high lipid-induced liver metastasis through the AKT and ERK pathways in vitro in breast cancer cells and in a mouse xenograft model

Abstract

Emodin, a natural anthraquinone derivative, can inhibit lipid synthesis and breast cancer cell proliferation. We previously found that emodin decreased breast cancer liver metastasis via epithelial-to-mesenchymal transition (EMT) inhibition. However, the mechanism through which emodin affects breast cancer liver metastasis in high-fat diet-induced obese and hyperlipidemic mice has not been elucidated. Bioinformatics analysis was used to reveal the potential targets and pathways of emodin. The mouse model of liver metastasis was established by injecting breast cancer cells into the left ventricle in high-fat diet-induced obese mice. The effect of emodin on inhibiting liver metastasis of breast cancer was evaluated by animal experiments. The mechanisms through which emodin inhibits liver metastasis of breast cancer were studied by cell and molecular biological methods. Emodin reduced lipid synthesis by inhibiting the expression of triglyceride (TG) synthesis-related genes, such as fatty acid synthase (Fasn), glycerol-3-phosphate acyltransferase 1 (Gpat1), and stearoyl-CoA desaturase (Scd1), and ultimately reduced liver metastasis in breast cancer. In addition, emodin inhibited breast cancer cell proliferation and invasion through the serine/threonine kinase (AKT) signaling and extracellular-regulated protein kinase (ERK) pathways by interacting with CSNK2A1, ESR1, ESR2, PIM1 and PTP4A3. Our results indicate that emodin may have therapeutic potential in the prevention or treatment of breast cancer liver metastasis.