Manganese‐12 acetate suppresses the migration, invasion, and epithelial–mesenchymal transition by inhibiting Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer cells

BACKGROUND: Breast cancer is the leading cause of cancer‐related death in the world, and it is of great value to reveal the molecular mechanisms of breast cancer progression and develop new therapeutic targets. METHODS: Transwell assay is used to analyze the migration and invasion of breast cancer cells. Real‐time PCR and western blotting assay are applied to detect the expression levels of epithelial–mesenchymal transition markers and the key members of Wnt/β‐catenin and PI3K/AKT signaling pathways. RESULTS: Manganese‐12 acetate (Mn12Ac) significantly inhibited the migration and invasion of MCF7 and MDA‐MB‐231 breast cancer cells. Western blotting assay further showed that Mn12Ac significantly upregulated E‐cadherin, and downregulated N‐cadherin and vimentin. We further found that Mn12Ac reduced the mRNA expressions of epithelial–mesenchymal transition‐associated transcription factors snail, slug, twist1, and ZEB1 using real‐time PCR assay. Importantly, we further found that Mn12Ac significantly reduced the Wnt1 and β‐catenin protein expressions, and suppressed the phosphorylation of PI3K and AKT in MCF7 and MDA‐MB‐231 breast cancer cells. Very interestingly, we also showed that Mn12Ac decreased the mRNA and protein expressions of programmed cell death ligand 1. CONCLUSION: Taken together, our results suggested that Mn12Ac inhibited the migration, invasion, and epithelial–mesenchymal transition by regulating Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer.