Chronic Unpredictable Mild Stress Accelerates the Growth of Bladder Cancer in a Xenograft Mouse Model

Abstract

Objective

Chronic psychological stress is common in patients with bladder cancer. An increasing number of evidence demonstrated that psychiatric disorder leads to worse prognostic outcomes in bladder cancer. This study was to investigate the effects of chronic psychological stress on the growth of bladder cancer and its potential mechanisms.

Methods

A xenograft mouse model was established by subcutaneously implanting the human bladder cancer cell line T24 into nude mice. All of the tumor-bearing mice (N=20) were randomly separated into two groups. Mice in the control group were subjected to normal feeding conditions, while in another group, a chronic unpredictable mild stress (CUMS) model was established, in which mice were exposed to various types of stressors. Various analyses were performed on parameters including the tumor volume, tumor weight, expression of Caspase-3 and VEGF, proportion of Ki-67 positive cells (Ki-67 index), microvessel density (MVD) and serum concentrations of epinephrine and cortisol.

Results

In the CUMS group, the growth of transplanted tumors was distinctly accelerated, with the weight of removed tumors at the end of experiment increased by 34.07% compared to that of the control. Serum levels of epinephrine and cortisol determined by ELISA were significantly increased by CUMS. Immunohistochemistry and Western blot analysis showed that the expression of Caspase-3 was downregulated, whereas the expression of VEGF was upregulated in the CUMS group. Meanwhile, CUMS could increase the Ki-67 index and MVD.

Conclusion

Our research supports the hypothesis that CUMS could affect the growth of bladder cancer in nude mice, indicating that the intervention of chronic psychological stress may be a possible therapeutic strategy for bladder cancer.