Topiramate inhibits the proliferation of bladder cancer cells via PI3K/AKTR signaling pathway

Purpose: To explore new treatment options for bladder cancer (BC) based on topiramate (TPM).Methods: The MTT assay and flow cytometry were used to determine the effect of topiramate on partial growth-related malignant phenotype of BC cells. Expression levels of apoptosis-related biomarkers and signaling pathway-related factors were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. In vivo experiments were conducted to investigate the role of TPM on tumor growth in mice with bladder cancer.Results: The MTT results showed that topiramate blocked the growth of BC cells (p < 0.05). Growth inhibition was positively correlated with TPM concentration. Flow cytometry results revealed that bladder cancer cell apoptosis rose with increase in TPM concentration, while the mRNAs of apoptosisassociated factors Bcl-2 and Mcl-1 were down-regulated in a concentration-based manner by TPM (p < 0.05). Western blot assay indicated that Bax and Caspase-3 proteins were up-regulated, and the higher the concentration of TPM, the more significant the protein expression levels (p < 0.05).Conclusion: Topiramate (TPM) slows down the rate of growth of BC cells and accelerates their rate of apoptosis through the regulation of P13K/AKT/mTOR signaling pathway. Thus, the compound has potentials for development as an anti-bladder cancer agent.