Modulation of resistance to cisplatin by amphotericin B and aphidicolin in human larynx carcinoma cells.
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.
Beketic-Oreskovic
L
L
Ruder Boskovic Institute, Department of Molecular Medicine, Zagreb, Croatia.
Osmak
M
M
D000666:Amphotericin B / Q000494:pharmacology*; D016590:Aphidicolin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014410:Tumor Stem Cell Assay
D016590:Aphidicolin; D000666:Amphotericin B; D016572:Cyclosporine; D002945:Cisplatin