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Inhibitory Effect of Ajuga decumbens Iridoids on the Metastasis of Triple Negative Breast Cancer and Its Related Mechanism

??OBJECTIVE To investigate the effect of iridoids in Ajuga decumbens(ADI) on the metastasis of invasive breast cancer cells and related mechanisms. METHODS Several assays including cell-HUVEC adhesion assay were conducted, Transwell migration and Transwell invasion assay were conducted. In vivo antimetastatic effect of ADI was determined using experimental lung metastatic models induced by tail vain injection of 4T1-luc cells. Western blot analysis was employed to detect the expression of associated proteins of EMT and ERK1/2 MAPK signaling pathway. RESULTS The 50-200 mgL^-1 ADI could significantly inhibit the cell-HUVEC adhesion, migration and invasion of MDA-MB-231 cells. Administration with 200 mgkg ^-1 dose of ADI markedly inhibited the lung tumor nodules. Treatment with ADI resulted in markedly inhibition of phosphorylation of ERK1/2 and the reversal EMT of breast cancer cells, which increased the levels of epithelial biomarkers, such as E-cadherin and ZO-1, and reduced the levels of mesenchymal biomarkers, such as vimentin. CONCLUSION These results indicates that ADI can inhibit breast cancer cell invasion by suppressing the ERK1/2 MAPK pathway as well as reversing the epithelial-mesenchymal transition.