Reversal of carboplatin resistance in human laryngeal carcinoma cells.
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.
Vuković
L
L
Department of Molecular Genetics, Ruder Bosković Institute, Zagreb, Croatia.
Osmak
M
M
D000666:Amphotericin B / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016590:Aphidicolin / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004976:Ethacrynic Acid / Q000494:pharmacology; D006801:Humans; D007822:Laryngeal Neoplasms; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016590:Aphidicolin; D019328:Buthionine Sulfoximine; D000666:Amphotericin B; D016572:Cyclosporine; D016190:Carboplatin; D004976:Ethacrynic Acid