Introduction

This study aimed to explore the antitumor effects of dexmedetomidine (Dex) in bladder cancer, focusing on its role in modulating ferroptosis and the tumor immune microenvironment.

Material and methods

Bladder cancer cell lines (T24 and RT4) were treated with various concentrations of Dex, followed by analysis of cell proliferation, ferroptosis markers, and immune evasion factors. In vivo, a mouse xenograft model of bladder cancer was used to assess tumor growth and related molecular mechanisms. Western blotting, flow cytometry, immunohistochemistry, and ELISA were used to evaluate protein expression levels, immune cell activity and cytokine production.

Results

Dex significantly inhibited bladder cancer cell proliferation and promoted ferroptosis by increasing intracellular Fe2+ and ROS levels. Dex also downregulated the ferroptosis-related proteins GPX4 and SLC7A11, disrupting the antioxidant defenses of bladder cancer cells. Furthermore, Dex inhibited immune evasion by reducing PD-L1 expression and enhancing CD8+ T-cell activity. Additionally, Dex suppressed the Wnt/β-catenin pathway by reducing active β-catenin, cyclin D1, and c-Myc levels. Dexmedetomidine significantly reduced tumor volume and weight in a T24 xenograft mouse model, reduced GPX4 and PD-L1 expression, increased IFN-γ levels, and suppressed Wnt/βcatenin pathway components.

Conclusions

Dexmedetomidine exerted antitumor effects in bladder cancer by inducing ferroptosis and modulating the tumor immune microenvironment through suppression of the Wnt/β-catenin signaling pathway. These findings suggested that Dex could be a promising therapeutic agent for bladder cancer, particularly in combination with immunotherapy strategies.