Dexamethasone induces partial resistance to cisplatinum in C6 glioma cells.
Malignant glioma patients are sometimes treated with cisplatinum (CDDP) and dexamethasone (DEX). The question, was addressed as to whether DEX induces cellular resistance to CDDP using the C6 glioma cell line in MTT-tests. 50% of the cells were killed by 2 x 10(-5) M, 5 x 10(-6) M, and 7 x 10(-7) M CDDP after 2, 24, and 72 hours of incubation, respectively. 10-6M DEX treatment protected C6 cells from CDDP 5 x 10(-5) M 72 hours, resulting in twice as many surviving cells, [p<0.01(t-test)]. This protection was also observed in human TE671 rhabdomyosarcoma and T98G human glioma cells but not in A172 human glioma cells. It was mediated by glucocorticoid receptors and increased glutathione. DEX reduced the sensitivity of C6 cells also to carboplatinum, doxorubicin, actinomycin D, cytosine-arabinoside and methotrexate but not to 4-hydroxyifosfamide, vincristine, radiation, 6-mercaptopurine or thioguanine. These data suggest a more restricted use of DEX during chemotherapy of brain tumour patients.
Wolff
J E
JE
University Hospital of Münster, Department of Pediatric Oncology, Germany.
Denecke
J
J
Jürgens
H
H
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000188:drug therapy; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy; D051381:Rats; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D003907:Dexamethasone; D005978:Glutathione; D002945:Cisplatin