Berberine Affects the Proliferation, Migration, Invasion, Cell Cycle, and Apoptosis of Bladder Cancer Cells T24 and 5637 by Down-Regulating the HER2/PI3K/AKT Signaling Pathway

To assess the anticancer effect, target, and mechanism of berberine on bladder cancer.Bladder cancer T24 and 5637 cells were treated with different concentrations of berberine. Then, cell proliferation was assessed by cell counting kit-8 (CCK8) measure, cell migration and invasion were assessed by transwell method, cell cycle and apoptosis were assessed by flow cytometry, and the expression of human epidermal growth factor receptor-2/PhosphoInositide-3 Kinase/AKT Serine/Threonine Kinase (HER2/PI3K/AKT) proteins were assessed by Western blot. Berberine molecular docking and HER2 target were performed using the AutoDock Tools 1.5.6. Finally, HER2 inhibitors CP-724714 and berberine were used independently or in combination to detect AKT and P-AKT protein downstream changes by Western blot.Berberine inhibited the proliferation of T24 and 5637 bladder cancer cells in a concentration-dependent and time-dependent manner. Berberine can significantly inhibit the migration, invasion, and cell cycle progression of T24 and 5637 bladder cancer cells, promote their apoptosis, and down-regulate the expression of HER2/PI3K/AKT proteins. Berberine showed good docking with HER2 molecular target and had a similar and synergistic effect with HER2 inhibitor in T24 and 5637 bladder cancer cells.Berberine inhibited the proliferation, migration, invasion, and cell cycle progression of T24 and 5637 bladder cancer cells and promoted their apoptosis by down-regulating HER2/PI3K/AKT signaling pathway.