Effect of PSC 833 on the efficacy of doxorubicin in vitro in a medullary thyroid carcinoma cell line.
In medullary carcinoma of the thyroid (MTC), multidrug resistance (MDR) remains the major obstacle to effective chemotherapy. In this work MDR was investigated in TT cells, a human MTC cell line. We studied the effect of an efficient MDR agent (SDZ PSC 833) on doxorubicin (DOX)-induced cytotoxicity in TT cells cultured in monolayers. The toxicity was evaluated with four tests: MTT test, lacticode-hydrogenase and glutathione assays, and neutral red uptake. PSC 833 (3 microM) partially reversed the resistance to DOX in vitro after a 48-hour coincubation, followed by a 24 hour-post incubation. Under these conditions, PSC 833 was not toxic at the concentration used. Our results suggest that PSC 833 has the potential to reverse the MDR phenotype in MTC cells.
Laboratoires de Génétique Moléculaire et Hormonologie, CHU de Pontchaillou, Rennes, France.
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Massart
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Gibassier
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Denais
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Genetet
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D018276:Carcinoma, Medullary / Q000188:drug therapy*; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D003524:Cyclosporins; D004317:Doxorubicin; C070272:valspodar