Related Experiment Videos
Dexamethasone reverses glucocorticoid receptor RNA depression in multi-drug resistant (MDR) myeloma cell lines
L Danel-Moore1, M Brönnegard, J A Gustafsson
1Department of Human Biological Chemistry and Genetics, University Texas Medical Branch, Galveston 77550.
Abstract:
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.
Insights
Doxorubicin resistance in myeloma cells correlates with lower glucocorticoid receptor RNA (GR RNA). Dexamethasone treatment reversed this resistance in some cell lines, suggesting steroids may help maintain tumor sensitivity to chemotherapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Multi-drug resistance (MDR) is a significant challenge in cancer chemotherapy.
- Glucocorticoids are used in treating multiple myeloma, but resistance can develop.
- The role of glucocorticoid receptors (GR) in MDR is not fully understood.
Purpose of the Study:
- To investigate the relationship between doxorubicin resistance and glucocorticoid sensitivity in myeloma cell lines.
- To examine the levels of glucocorticoid receptors (GR) and GR RNA in drug-resistant cells.
- To assess the effect of dexamethasone on GR RNA levels in resistant cell lines.
Main Methods:
- Measurement of glucocorticoid receptors and GR RNA in doxorubicin-resistant (R10, R40, R60) and wild-type RPMI 8226 myeloma cell lines.
- Treatment of cell lines with dexamethasone (10(-6) M) for 48 hours.
- Comparison of GR RNA levels between treated and untreated cells, and between resistant and wild-type lines.
Main Results:
- Doxorubicin-resistant cell lines (R10, R40, R60) showed lower GR RNA levels compared to wild-type cells.
- The R10 cell line, despite low GR RNA, remained sensitive to dexamethasone.
- Dexamethasone treatment increased GR RNA levels in the highly resistant R40 and R60 cell lines, overcoming doxorubicin-induced downregulation.
Conclusions:
- Reduced GR RNA is associated with doxorubicin resistance in myeloma cells.
- Dexamethasone can potentially reverse or overcome doxorubicin resistance by modulating GR RNA levels.
- Steroids may be a valuable therapeutic strategy for maintaining tumor cell sensitivity to chemotherapy.