title: The effect of ultrasonic irradiation on doxorubicin-induced cytotoxicity in three human bladder cancer cell lines.
abstract: 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 MTS 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 5min and 10min at an intensity of approximately 0.3W/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.
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Arthur
authors.forename: Thomas
authors.initials: T
authors.lastname: Flaig
authors.forename: Lih-Jen
authors.initials: LJ
authors.lastname: Su
authors.forename: Richard
authors.initials: R
authors.lastname: Denney
authors.forename: Frank
authors.initials: F
authors.lastname: Barnes
authors.forename: L Michael
authors.initials: LM
authors.lastname: Glodé
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use*; D006801:Humans; D016896:Treatment Outcome; D014463:Ultrasonography; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin