In-vitro effects of taurolidine alone and in combination with mitoxantrone and/or piroxicam on canine transitional cell carcinoma

摘要

The objective of this in-vitro study was to evaluate taurolidine as a therapy for transitional cell carcinomas in canine patients. Transitional cell carcinoma (TCC) is the most common cancer of the urinary bladder in dogs and accounts for approximately 2% of reported malignancies in this species. There is no cure for this neoplasm and most dogs are lost from complications associated with progression of the local disease. Taurolidine has been shown to have anti-tumor and antiangiogenic effects against a variety of neoplasms in human and animal models. Four canine TCC cell lines were treated with various concentrations of taurolidine, mitoxantrone, and piroxicam alone. In addition, combinations of taurolidine/mitoxantrone, taurolidine/piroxicam, mitoxantrone/piroxicam, and taurolidine/mitoxantrone/piroxicam were assessed. Susceptibility of the TCC cell lines was based on a 72-hour growth inhibition assay using resazurin with absorbance measured at λ530/590. The ability of taurolidine to induce apoptosis was evaluated on 2 of the cell lines with an Annexin-V/propidium iodide assay. All cell lines were susceptible to treatment with taurolidine, mitoxantrone, and piroxicam alone. The results of the combination therapies of the 3 drugs were dependent on cell line and concentration and revealed no change in cell growth inhibition, a subadditive relationship, or a synergistic relationship. Taurolidine induced apoptosis in a concentration- and time-dependent fashion. Taurolidine alone showed significant effects on cell viability in vitro in canine TCC cell lines and these effects can be potentially enhanced with the addition of mitoxantrone and/or piroxicam.