Role of NF-κB in the Rescue of Multiple Myeloma Cells From Glucocorticoid-Induced Apoptosis by Bcl-2

摘要: The molecular mechanisms by which multiple myeloma (MM) cells evade glucocorticoid-induced apoptosis have not been delineated. Using a human IgAκ MM cell line (ARP-1), we found that dexamethasone (Dex)-induced is associated with decreased NF-κB DNA binding and κB-dependent transcription. Both nuclear p50:p50 p50:p65 complexes are detected in ARP-1 supershift electrophoretic mobility shift assay (EMSA). Dex-mediated inhibition of precedes notable increase annexin V binding, thereby indicating diminished activity an early event Dex-induced apoptosis. Overexpression bcl-2 prevents repression Sustained also observed two previously characterized Dex-resistant lines (RPMI8226 ARH-77) express moderate levels endogenous IκB proteins. In addition, enforced expression did prevent the augmentation protein Dex. We noted possible association between downregulation freshly obtained primary patients’ responsiveness to glucocorticoid-based chemotherapy. Collectively, our data suggest protective effects act upstream activation–signaling pathway potential use as biomarker progressive MM.