In-Vitro Effects of Recombinant IL-37 protein on Bladder cancer cell line Growth and Proliferation

Abstract

Introduction: Interleukin-37 (IL-37) is a cytokine of the IL-1 family, recognized for its anti-inflammatory and immunomodulatory functions. Despite growing interest in IL-37’s role in different types of cancers, its impact on bladder cancer growth and proliferation has not been thoroughly investigated. This study aims to explore the effects of recombinant IL-37 protein on the viability, proliferation, and apoptosis of T24 bladder cancer cell lines, addressing a significant gap in current cancer research. Methods: In this in vitro study, T24 bladder cancer cells were treated with different concentrations of recombinant IL-37 protein (1 μg/ml, 0.5 μg/ml, and 0.25 μg/ml) with negative control (0 μg/ml). Cell viability and apoptosis were assessed using flow cytometry, and the levels of pro- inflammatory cytokines IL-6 and IL-8 in the cell culture supernatants were quantified using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test to determine the significance of the results. Results: The results showed that IL-37 induces apoptosis in a dose-dependent manner, with the highest concentration (1 μg/ml) significantly reducing the percentage of viable cells from 90% to 71% and increasing the apoptotic cell population from 7% to 27%. Additionally, IL-37 treatment modulated the secretion of IL-6 and IL-8, with a significant increase in IL-6 production at 0.25 μg/ml (P ≤ 0.05) compared to the control. However, IL-37 did not significantly inhibit IL-8 production across the different treatment groups. (P ≤ 0.05). Conclusion: This study demonstrates that IL-37 not only promotes apoptosis in bladder cancer cells but also alters the tumor microenvironment by modulating cytokine secretion. These findings suggest that IL-37 may hold therapeutic potential as a novel approach to bladder cancer treatment. Further research is necessary to validate these results in vivo and to elucidate the precise molecular mechanisms through which IL-37 exerts its anti-tumor effects.