Chemosensitisation of a drug-sensitive parental cell line by low-dose cyclosporin A.
We investigated the chemosensitisation of the parental EMT6 mouse mammary tumour cell line by low doses of cyclosporin A (CsA). This cell line has not previously been exposed to cytotoxic drugs but expresses low levels of P-glycoprotein. We produced greater than 2-fold sensitisation to doxorubicin, colchicine and vincristine using 0.084 microM (0.1 micrograms/ml) CsA. Cellular accumulation of doxorubicin and daunorubicin was also increased by this dose. In the MDR subline EMT6/AR1.0, much higher doses of CsA were required to effect optimal restoration of doxorubicin or daunorubicin accumulation. The effects of CsA on the parent line could not be increased by extended preincubation of cells with the sensitiser. These effects of CsA in the EMT6 parent cell line occur at a dose that is 1 order of magnitude lower than those previously reported to produce significant chemosensitisation.
Twentyman
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PR
MRC Clinical Oncology, Cambridge, UK.
Wright
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KA
D000818:Animals; D002296:Carcinosarcoma / Q000188:drug therapy / Q000378:metabolism; D002460:Cell Line; D003078:Colchicine / Q000493:pharmacokinetics / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014750:Vincristine / Q000493:pharmacokinetics / Q000627:therapeutic use
D014750:Vincristine; D004317:Doxorubicin; D016572:Cyclosporine; D003078:Colchicine