Effect of low‐energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer

Abstract

To study the efficacy of low-energy shock wave therapy (LESW) on enhancing intravesical epirubicin (EPI) delivery in a rat model of bladder cancer (BCa). Materials and Methods A total of 100 female Fischer rats were randomly allocated into five groups: control; BCa; LESW; EPI; and EPI plus LESW. After BCa 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 1 h with or without LESW treatment (300 pulses at 0.12 mJ/mm 2). This was repeated weekly for 6 weeks. Survival was then calculated, rats were weighed and their bladders were harvested for bladder/body ratio estimation, histopathological examination, p 53 immunostaining, miR-210, hypoxia-inducible factor (HIF)-1α, tumour necrosis factor (TNF)-α and interleukin (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 The EPI plus LESW group had significantly lower mortality rates, loss of body weight and bladder/body ratio. Histopathological results in terms of grossly visible bladder lesions, mucosal thickness, dysplasia formation and tumour invasion were significantly better in the combined treatment group. The EPI plus LESW group also had statistically significant lower expression levels of p 53 , miR-210, HIF-1α, TNF-α and IL-6. LESW increased urothelial concentration of EPI by 5.7-fold (P < 0.001). No laboratory variable exceeded the reference ranges in any of the 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 the EPI plus LESW group. Conclusions The combined use of intravesical EPI and LESW results in less BCa invasion and less dysplasia formation, as LESW increases urothelial permeability of EPI and enhances its delivery into tumour tissues, without subsequent toxicity.

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment

“…The combination of intravesical epirubicin and LESW results in reduced cancer cell invasion and urothelial cell dysplasia. In that study, LESW was shown to increase urothelial permeability and enhance the delivery of the drug into tumor tissues without subsequent toxicity [ 86 ].…”

Extracorporeal Shock Wave Enhances the Cisplatin Efficacy by Improving Tissue Infiltration and Cellular Uptake in an Upper Urinary Tract Cancer Animal and Human-Derived Organoid Model

“…Some studies have focused on improving the focal permeability of macromolecular cytotoxic drugs into specific cancer tissue [ 32 ]. For example, some studies have reported that LESW combined with chemotherapy can improve the treatment efficacy of chemotherapy by increasing the intracellular drug concentration [ 28 , 33 ]. In this study, we observed a similar result in vitro and in vivo and further identified decreased expression of the tight junction protein ZO-1 and the adherent junction protein E-cadherin when chemotherapy was used in combination with LESW.…”

Low-energy shock waves promote the cisplatin chemosensitivity of human osteosarcoma MNNG/HOS cells via the P2X7/Akt/mTOR pathway

“…SWs introduce a great positive pressure, further increase the mammalian cell membrane permeability, and transiently induce membrane pore formation, thus allowing macromolecular drugs to enter cells and elicit their therapeutic effects 5 . Currently, SWs are known to enhance the cytotoxicity of chemotherapeutic drugs in several types of carcinoma, including breast 6 , bladder 7 , and prostate cancers 8 , although SWs alone show little inhibitory influence on tumour growth. In a Mat B-III syngeneic rat breast cancer model, SWs and the chemical protoporphyrin IX have been demonstrated to decrease the tumour size with stronger necrotic and apoptotic clinical histological features compared to protoporphyrin IX alone 6 .…”

“…In a Mat B-III syngeneic rat breast cancer model, SWs and the chemical protoporphyrin IX have been demonstrated to decrease the tumour size with stronger necrotic and apoptotic clinical histological features compared to protoporphyrin IX alone 6 . In addition, low-energy SWs have been shown to promote intravesical epirubicin delivery in bladder cancer, followed by reduced metastasis and dysplasia formation 7 . Moreover, SW treatment has been reported to inhibit the activation of cancer-associated fibroblasts as well as to decrease androgen-resistant prostate cancer cell growth and invasion 8 .…”