Abstract

Chemotherapy remains the main treatment for muscle-invasive bladder cancer (BLCA) despite drug resistance and lack of target drugs greatly limiting long-term survival of patients. Thus, novel and effective drugs specific to BLCA are required to aid in its treatment and improve patient survival. In the present study, we found that the compound Ro-31-8220, a pan-protein kinase C inhibitor, displays potent anti-bladder cancer efficacy in vitro and in vivo. Ro-31-8220 treatment suppressed bladder cancer cell migration and invasion and also induced cell apoptosis in a dose-dependent manner. Proteomic analysis showed that Ro-31-8220 treatment altered the expression of numerous proteins and KEGG enrichment analysis demonstrated that multiple signal pathways are regulated by Ro-31-8220, including autophagy. To further validate these results, we carried out western blotting, GFP-LC3 fusion protein and transmission electron microscopy analyses, all of which demonstrated that Ro-31-8220 induced bladder cancer cell autophagy. Blockade of autophagy with chloroquine, an autophagy inhibitor, attenuated Ro-31-8220 induced bladder cancer cell death. In a bladder cancer xenograft tumor growth mice model, we showed that intraperitoneal injection of Ro-31-8220 significantly decreased tumor size and tumor weight compared to the control group, suggesting an in vivo tumor suppression ability of Ro-31-8220 through activation of autophagy. These results suggest that Ro-31-8220 may be a novel promising candidate drug for bladder cancer therapy. Further studies, including clinical trials, are required to validate these results.