Glucocorticoid effects on myeloma cells in culture : correlation of growth inhibition with induction of glucocorticoid receptor messenger RNA

摘要: Glucocorticoids are widely used for the treatment of multiple myeloma. To investigate direct actions glucocorticoids on myeloma cells, we have three cell lines human myeloma, OPM-1, OPM-2, and RPMI 8226. When growth curves these cells were examined, OPM-1 resistant, while OPM-2 sensitive to dexamethasone (DEX). In cultures addition DEX led virtual cessation growth, with only 16% residual viable after 4 days. 8226 appeared be slightly sensitive, showing some slowing several days in DEX, later recovery. Viabilities not affected. Secretion immunoglobulin (Ig-lambda) was also partially suppressed, by 30% 14% OPM-1. No significant suppression observed explore mechanism differential responses steroid, glucocorticoid receptor (GR) examined. Binding assays showed high affinity binding sites all lines: 64 +/- 11 fmol/10(6) 78 14 62 16 Nuclear transfer GR DNA-cellulose heat activation similar lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis cytosol proteins labeled [3H]dexamethasone mesylate a Mr 95,000 three. mRNA studied them had approximately 7 kilobases, but 3 times more than induced 2-fold at 5 x 10(-9) M or greater. much less no response 10(-6) 1.5-fold induction that concentration. These results demonstrate can killed action glucocorticoids. The quantity predictive this response. Therefore, propose resistance relative inhibition is post-receptor mechanisms. sensitivity may correlate glucocorticoid-evoked kill.