Effect of Low Energy Shock Wave Therapy on Intravesical Epirubicin Delivery in a Rat Model of Bladder Cancer

OBJECTIVES To study the efficacy of low energy shock wave (LESW) on enhancing intravesical epirubicin (EPI) delivery in a rat model of bladder cancer (BC). MATERIALS AND METHODS 100 female Fischer rats were randomly allocated into five groups; Control, BC, LESW, EPI and EPI plus LESW groups. After BC induction by N-butyl-N-(4-hydroxybutyl)nitrosamine, EPI (0.6 mg/0.3 ml of EPI diluted in 0.3 ml saline) or saline (0.6 ml) was administered and retained in the bladders for one hour with or without LESW treatment (300 pulses at 0.12 mJ/mm2 ). This was repeated weekly for six weeks. Survival was then calculated, rats were weighed and their bladders were harvested for bladder/body ratio estimation, histopathological examination, p53 immunostaining, miR-210, HIF-1α, TNF-α and IL-6 relative gene expression and fluorescence spectrophotometric drug quantification. Heart and blood samples were also collected for assessment of the safety profile and toxicity. RESULTS EPI plus LESW group showed significantly lower mortality rates, loss in body weights and bladder/body ratios. Histopathological results in terms of grossly visible bladder lesions, mucosal thickness, dysplasia formation and tumor invasion were significantly better in the group of combined treatment. EPI plus LESW group also showed statistically significant lower expression levels of p53 , miR-210, HIF-1α, TNF-α and IL-6. LESW increased urothelial concentration of EPI by 5.7 folds (p <0.001). All laboratory parameters did not exceed the reference ranges in all groups. There was an improvement of the indicators of EPI-induced cardiomyopathy in terms of congestion, hyalinization and microvesicular steatosis of cardiomyocytes (p = 0.068, 0.003 and 0.046, respectively) in EPI plus LESW group. CONCLUSIONS The combined use of intravesical EPI and LESW results in less BC invasion and less dysplasia formation, as LESW increases urothelial permeability of EPI and enhances its delivery into tumor tissues, without subsequent toxicity.