Mesenchymal Stem Cells Inhibit the Effects of Dexamethasone in Multiple Myeloma Cells

Abstract

Mesenchymal stem cells (MSCs) participate in the occurrence and development of multiple myeloma. This study is aimed at exploring whether the presence of MSCs affects dexamethasone’s antitumor effects against multiple myeloma. Multiple myeloma cells (OPM-2 and RPMI8226 cells) were cocultured with MSCs with or without dexamethasone. Cell viability was determined by using cell number count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and colony formation assay, respectively. Cell cycle distribution and cell apoptosis were evaluated by using flow cytometry. The mRNA and protein expressions of target genes were checked by using qRT-PCR and western blotting, respectively. It was found that cell viability of multiple myeloma cells increased in the presence of MSCs. Besides, the presence of MSCs suppressed cell apoptosis induced by dexamethasone via the regulation of BCL-2 (B cell lymphoma 2). The presence of MSCs also affected the effects of dexamethasone on cell cycle distribution. Similarly, LINC00461 overexpression suppressed the inhibition of cell proliferation, suppressed the induction of cell apoptosis, and affected the effects on cell cycle distribution induced by dexamethasone insult. However, LINC00461 knockdown enhanced the inhibitory effects on cell proliferation and the induction of cell apoptosis induced by dexamethasone. In summary, MSCs inhibited the effects of dexamethasone on multiple myeloma and its regulatory effects were associated with LINC00461.

A Journey through the Inter-Cellular Interactions in the Bone Marrow in Multiple Myeloma: Implications for the Next Generation of Treatments

“…Moreover, MSC-derived exosomes contain the long intergenic noncoding RNA LINC00461, which promotes MM cell proliferation and suppresses the beneficial effect of dexamethasone treatment. Indeed, the knockdown of LINC00461 enhances the beneficial impact of dexamethasone in preclinical studies [ 48 ].…”

“…In summary, these interleukins and growth factors secreted by BM-MSCs cause tumor growth and drug resistance, limiting current MM treatments’ impact. Indeed, they are promising targets for developing anti-MM therapies that avoid the negative effect of BM-MSCs on dexamethasone treatment [ 48 ], on CAR-T cell therapies [ 53 ], or the negative impact of IL6 secretion. Thus, tocilizumab, an anti-IL6R [ 57 ], BHQ880, a monoclonal antibody against DKK1 [ 58 ], or tabalumab, a potent and selective fully human IgG4 MoAb with neutralizing activity against membrane-bound and soluble BAFF [ 59 ] are strategies that could be added to MM treatment.…”