Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Liu Chao, Shaoqi Zhang, Jianjun Zhang, Longjun Cai, Xiangyu Wang, Fanlai Meng, Weiqi Cai

Department of Urology Surgery, Nanjing Drum Tower Hospital Group Suqian Hospital, The Suqian Affiliated Hospital of Xuzhou Medical University School, Suqian City, Jiangsu Province 223800, China;

For correspondence:- Weiqi Cai Email: fnaj3i@163.com

Accepted: 28 March 2022 Published: 28 April 2022

Citation: Chao L, Zhang S, Zhang J, Cai L, Wang X, Meng F, et al. Topiramate inhibits the proliferation of bladder cancer cells via PI3K/AKTR signaling pathway. Trop J Pharm Res 2022; 21(4):685-691 doi: 10.4314/tjpr.v21i4.1

© 2022 The authors.
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Abstract

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 apoptosis-associated 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.

Keywords: Topiramate, Bladder cancer, Proliferation, Apoptosis, PI3K/AKT/mTOR