The effect of ultrasonic irradiation on doxorubicin-induced cytotoxicity in three human bladder cancer cell lines

Although ultrasonic irradiation has been proven to increase membrane permeability and enhance chemotherapeutic cytotoxicity in a number of cell lines, this effect has never been demonstrated in bladder cancer cells. Bladder cancer may offer a unique setting for ultrasound enhancement of chemotherapy, since intravesicular rather than intravenous administration of chemotherapy is used in superficial cases. The aim of this study was to investigate whether a non-toxic dose of ultrasound could increase membrane permeability, and potentiate the cytotoxicity of doxorubicin to three human bladder carcinoma cell lines (TCC-SUP, T24, and RT4) in vitro. An EuTDA-Efflux assay, which measures the amount of a chemical that is allowed to seep out of labeled cells, was used to analyze membrane permeability, and an NITS assay, which directly measures cell viability, was used to determine the effect of chemotherapy on cells after they were treated with a variety of doxorubicin concentrations and ultrasonic exposures. Ultrasound treatment for 5 min and 10 min at an intensity of approximately 0.3 W/cm(2) resulted in a significant increase in EuTDA efflux in all three cell lines. However, no ultrasonic enhancement of doxorubicin growth inhibition in these human bladder carcinoma cells was observed. This suggests that either ultrasound does not increase doxorubicin uptake by the cell or that doxorubicin uptake is increased but in insufficient amounts to affect growth inhibition. Further investigation should focus on explaining these results. (c) 2006 Elsevier B.V. All rights reserved.