Dexamethasone reverses glucocorticoid receptor RNA depression in multi-drug resistant (MDR) myeloma cell lines.
Glucocorticoid receptors and glucocorticoid receptor RNA (GR RNA) were measured in doxorubicin resistant myeloma cell lines to investigate the relationship between multi-drug resistance and glucocorticoid sensitivity. Glucocorticoid binding sites and GR RNA were found to be lowered in all the tested doxorubicin resistant cell lines: R10, R40 and R60 compared to the untreated wild type RPMI 8226 cells (Dalton, et al., 1984). The least resistant cell line, R10, maintained a down regulation of GR RNA after 48 hours of dexamethasone (10(-6) M) treatment of the cells. Interestingly, the R10 cell line has been reported to be very sensitive to dexamethasone treatment. However, the GR RNA levels increased in presence of dexamethasone in the most resistant cell line, R40, R60 by comparison to the wild type. Thus, the reduction of GR RNA by doxorubicin treatment appears to be overcome by dexamethasone in the most resistant cell lines. Steroids may be helpful in reversing resistance and maintaining drug sensitive human tumor populations that will continue to respond to cancer chemotherapeutic agents.
Danel-Moore
L
L
Department of Human Biological Chemistry and Genetics, University Texas Medical Branch, Galveston 77550.
Brönnegard
M
M
Gustafsson
J A
JA
D003907:Dexamethasone / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D014407:Tumor Cells, Cultured
D012334:RNA, Neoplasm; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D004317:Doxorubicin