Effects of Platycodon grandiflorus on doxorubicin resistance and epithelial-mesenchymal transition of breast cancer cells via the p38 mitogen-activated protein kinase pathway

With the increase of chemotherapy frequency for breast cancer, the drug resistance rate of patients is rising, accompanied by cell invasion and metastasis, thus causing mortality. We aimed to explore the mechanism by which Platycodon grandiflorus affects breast cancer cells in terms of the doxorubicin (Dox) resistance and epithelial-mesenchymal transition (EMT) via the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MCF-7/R cell lines with resistance to Dox were established. After 24 h of culture with DMEM (blank group), they were divided into Platycodon grandiflorus, Platycodon grandiflorus + Ophiopogon japonicus, Platycodon grandiflorus + Curcumae Rhizoma, Platycodon grandiflorus + Curcumae Rhizoma + U46619 groups. Flow cytometry, colony formation assay, as well as Transwell assay were performed to examine the cells for apoptosis, proliferation, and invasion, respectively. Western blotting was performed to measure the phosphorylated (p)-p38 MAPK-to-p38 MAPK ratio together with N-cadherin, vimentin, β-catenin, and E-cadherin protein expressions. Compared with the blank group, the half maximal inhibitory concentration (IC₅₀), number of cell colonies, number of invading cells and expressions of proteins related to EMT (i.e. N-cadherin, vimentin, and β-catenin) significantly reduced, but increases in apoptosis rate, p-p38 MAPK/p38 MAPK ratio and E-cadherin protein expression were observed in different groups (P < 0.05). Compared with the Platycodon grandiflorus + Curcumae Rhizoma group, the Platycodon grandiflorus + Curcumae Rhizoma + U46619 group had significantly decreased IC₅₀, cell colony count, invading cell count and β-catenin, N-cadherin, and vimentin expressions, in addition to elevated E-cadherin protein expression, apoptosis rate, and p-p38 MAPK/p38 MAPK ratio (P < 0.05). Platycodon grandiflorus can reverse the resistance of breast cancer cells to Dox and regulate their biological activities by activating the p38 MAPK signaling pathway.