aphidicolin and Laryngeal-Neoplasms

The effectiveness of carboplatin in the treatment of patients with tumors is limited by drug resistance. Because of that, there is a great interest to find a way to revert the resistance and improve the success of cancer treatment. The aim of the present study was to examine five potential modulators of carboplatin resistance with different mode of action: buthionine sulfoximine, ethacrinic acid, amphotericine B, cyclosporine A and aphidicoline. The effect of these compounds on the sensitivity of human laryngeal parental (HEp2) and carboplatin-resistant (HEp7T) cells to carboplatin was examined by MTT spectrophotometric assay. The results have shown that buthionin sulfoximine and, to a lesser extent, ethacrinic acid reduced the resistance of HEp7T cells to carboplatin. Aphidicolin increased the sensitivity of both HEp2 and HEp7T cells to carboplatin, but this effect was more expressed in parental HEp2 cells. Our data suggest that human laryngeal carcinoma cells treated with clinically relevant doses of carboplatin became resistant to this drug due to multifactorial molecular mechanisms. Accordingly, the resistance to carboplatin could be reduced by different modulators.

Topics: Amphotericin B; Antineoplastic Agents; Aphidicolin; Buthionine Sulfoximine; Carboplatin; Cyclosporine; Drug Resistance, Neoplasm; Drug Synergism; Ethacrynic Acid; Humans; Laryngeal Neoplasms; Tumor Cells, Cultured

The aim of this study was to examine whether resistance to cisplatin [cis-diamminedichloroplatinum (II)] (CDDP) could be overcome by amphotericin B, cyclosporin A and aphidicolin in two sublines of human larynx carcinoma HEp2 cells. The sensitivity of parental and cisplatin-resistant CA3 and CK2 cells to amphotericin B, cyclosporin A and aphidicolin, and also the effects of these drugs (given in maximal nontoxic concentrations) on cisplatin sensitivity were determined by clonogenic survival assay. CA3 and CK2 cells were sensitive to amphotericin B, and resistant to cyclosporin A and aphidicolin, compared with their parental cells. Amphotericin B increased cisplatin toxicity 2-fold in CA3 cells and 2.7-fold in CK2 cells, while it had no effect in parental HEp2 cells. Cyclosporin A did not influence the sensitivity of examined cells to cisplatin. The sensitizing effect of aphidicolin was more obvious in cisplatin-resistant cells. Cisplatin toxicity was increased by aphidicolin: 1.5-fold in HEp2 cells, 2-fold in CA3 cells, and 1.9-fold in CK2 cells. Therefore, the resistance to cisplatin in human larynx carcinoma CA3 and CK2 cells can be partially reversed by amphotericin B and aphidicolin.

Topics: Amphotericin B; Aphidicolin; Cell Survival; Cisplatin; Cyclosporine; Drug Resistance; Humans; Laryngeal Neoplasms; Tumor Cells, Cultured; Tumor Stem Cell Assay