antimony-potassium-tartrate and Breast-Neoplasms

We have recently shown that high-level expression of the multidrug resistance-associated protein (MRP) gene is a powerful independent predictor of poor outcome in neuroblastoma. The clinical implication of these findings is that MRP modulators may prove therapeutically useful.. We therefore investigated the ability of difloxacin, a quinolone antimicrobial antibiotic, to increase drug cytotoxicity in unselected cultured human neuroblastoma cells. Drug cytotoxicity was determined using a microtiter assay in neuroblastoma cells expressing low (SH-EP), intermediate (NBL-S), or high [BE(2)-C] levels of MRP.. Difloxacin (50 microg/ml) increased sensitivity to the MRP substrates, vincristine, doxorubicin, daunorubicin, and potassium antimony tartrate to an extent directly proportional to their level of MRP expression. No change in the response to cisplatin, which is not a substrate for MRP, was observed in any of the cell lines.. The data demonstrate that difloxacin can reverse drug resistance in unselected human neuroblastoma cells and is therefore a potential candidate for future clinical trials.

Topics: Adenocarcinoma; Anti-Infective Agents; Antimony Potassium Tartrate; ATP-Binding Cassette Transporters; Breast Neoplasms; Ciprofloxacin; Cisplatin; Daunorubicin; Doxorubicin; Drug Evaluation, Preclinical; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Fluoroquinolones; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes, myc; Humans; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Neuroblastoma; Polymerase Chain Reaction; Substrate Specificity; Tumor Cells, Cultured; Vincristine