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Bim downregulation by activation of NF- κB p65, Akt, and ERK1/2 is associated with adriamycin and dexamethasone resistance in multiple myeloma cells
In this study, we examined the MDR mechanism in adriamycin- and dexamethasone-resistant cells. RPMI8226/ADM, ARH-77/ADM, RPMI8226/DEX, and ARH-77/DEX cells exhibited enhanced nuclear factor κB (NF-κB) p65, Akt, and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Combination treatment with NF-κB p65, phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinase 1/2 (MEK1/2) inhibitors resensitized to adriamycin and dexamethasone via increased Bim expression. A lthough treatment with MDR1 or Survivin siRNA did not overcome adriamycin and dexamethasone resistance in RPMI8226/ADM and RPMI8226/DEX cel...
Source: Clinical and Experimental Medicine - November 30, 2022 Category: Research Source Type: research

Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1
Abstract The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse d...
Source: Clinical and Experimental Medicine - January 29, 2015 Category: Research Source Type: research