[Erianin inhibits proliferation and migration of breast cancer cells by inhibiting Wnt/β-catenin signaling].

[OBJECTIVES] To investigate the effect of erianin on proliferation, migration, invasion, and apoptosis of breast cancer cells and the underlying mechanisms.

[METHODS] Breast cancer cell lines T-47D and MCF-7 treated with 0, 12.5, 25, 50, and 100 nmol/L erianin for 12, 24, 36, 48, and 72 h were examined for cell viability using CCK-8 assay. The effects of erianin on cell proliferation, migration, invasion, senescence and apoptosis were evaluated using clone formation, wound healing, Transwell invasion, and senescence assays and flow cytometry. mRNA microarray analysis and the Enrichr database were used to explore the biological functions of erianin. Western blotting was used to detect the changes in protein expressions related to apoptosis, epithelial-mesenchymal transition (EMT), and the Wnt/β-catenin pathway.

[RESULTS] Erianin concentration-dependently inhibited cell viability, proliferation, migration, and invasion, and promoted senescence in T-47D and MCF-7 cells. Microarray analysis identified 1064 differentially expressed genes (DEGs), including 948 upregulated and 116 downregulated genes, which were involved primarily in EMT regulation, collagen-containing extracellular matrix, calcium ion binding, the PI3K-Akt signaling pathway, the Wnt/β-catenin signaling pathway, and apoptosis. Flow cytometry confirmed that erianin concentration-dependently induced apoptosis in the breast cancer cells, upregulated the expressions of Bax and caspase-3, decreased Bcl-2 expression, and lowered the expressions of EMT-related proteins (Snail, N-cadherin, and β‑catenin) and Wnt/β‑catenin signaling proteins (TCF4, Cyclin D1, and c-Myc). In the breast cancer cells treated with 100 nmol/L erianin, the application of a Wnt/β‑catenin agonist significantly increased the proteins expressions of TCF4, Cyclin D1, and c-Myc.

[CONCLUSIONS] Erianin inhibits proliferation, migration, and invasion and induces senescence and apoptosis in breast cancer cells possibly by suppressing the Wnt/β-catenin signaling pathway to induce cell apoptosis and reverse EMT of the cells.