Andrographolide enhances the antitumor activity of cisplatin by inhibiting the PI3K/AKT signaling pathway in bladder cancer

Bladder cancer (BC) is the most common malignant tumor of urinary system worldwide. Resistance to cisplatin(CDDP) in advanced bladder cancer leads to reduced survival rates. Andrographolide(Andro), an active ingredient extracted from Andrographis paniculate, has been reported to have multidimensional pharmacological properties. Here we report the therapeutic effect of Andro and CDDP on BC. BIU87 Cisplatin resistant (BIU87-CISR) cells were exposed to Andro or CDDP in different concentrations in vitro. In vivo, the subcutaneous tumor bearing (BIU87-CisR cells) mouse model was constructed. The results indicated combination therapy of Andro and CDDP significantly inhibited BIU87-CisR cells proliferation, migration and invasion. Andro treatment alleviated epithelial-to-mesenchymal transition (EMT) in BIU87-CisR cells. Furthermore, the combination treatment enhanced inhibition of Andro on PI3K/AKT signaling pathway. The molecular docking was also used to support the above results. Taken together, Andro enhanced the effect of CDDP therapy by modulating PI3K/AKT signaling pathway to reduce EMT in cisplatin resistant bladder cancer cells. This study provides a theoretical basis for the clinical application of Andro as an adjuvant drug in the treatment of BC.