An evaluation of the effect of bortezomib on radiation-induced urinary bladder dysfunction

Abstract

Purpose: The urinary bladder is one major organ at risk in radiotherapy of pelvic malignancies. The radiation response manifests in early and chronic changes in bladder function. These are based on inflammatory effects and changes in urothelial cell function and proliferation. This study evaluates the effect of bortezomib as an anti-proliferative and anti-inflammatory compound in an established mouse bladder model. The early radiation-induced bladder dysfunction in the mouse occurs in two phases during the first month after irradiation (phase I: day 0-15, phase II: days 16-30).

Materials and methods: Daily bortezomib injections (0.02 mg/ml, subcutaneously) were administered between days 0-15 or 15-30 in separate groups. Single graded radiation doses were administered in five dose groups. Cystometry was carried out before (individual control) and during the first month after irradiation. When bladder capacity was decreased by ≥50%, mice were considered as responders. Statistical analysis was performed by the SPSS software version 24.

Results: Daily bortezomib injections between days 0-15 resulted in a significant decrease in responders for phase I. There was no significant effect with daily bortezomib injections between days 16-30.

Conclusion: Two separate waves of acute radiation-induced urinary bladder dysfunction have distinct mechanisms that need further biological studies.

Keywords: Cystometry; Mouse model; Pelvic neoplasms; Radiotherapy.