Decitabine enhances bortezomib treatment in RPMI 8226 multiple myeloma cells

Abstract

The present study investigated the interactions between decitabine (DAC) and bortezomib (BTZ) in RPMI 8226 multiple myeloma (MM) cells. Cells were exposed to DAC alone and in combination with BTZ for 48 h. A Cell Counting Kit‑8 assay was performed to assess the rate of proliferation inhibition in the cells. Cell apoptosis was investigated by Annexin V-fluorescein isothiocyanate and propidium iodide staining. Flow cytometry was used to detect the different cell cycle stages. Western blotting was performed to analyze the protein expression levels of poly(ADP‑ribose) polymerase 1 (PARP‑1), caspase‑3, ‑9 and DNA (cytosine‑5‑)‑methyltransferase 1 (DNMT1). Reverse transcription‑quantitative polymerase chain reaction was used to assess DNMT1 gene expression. The combination of DAC and BTZ increased the proliferation inhibition, apoptotic rate and G0‑G1 arrest compared with use of a single therapeutic agent. In addition, the combination treatment enhanced PARP‑1 cleavage, caspase‑3 and caspase‑9 activation and downregulated the protein and mRNA expression levels of DNMT1. Therefore, the current study determined that the combination of BTZ and the epigenetic agent DAC may be a novel therapeutic strategy to improve the efficacy of BTZ in patients with MM.

Lower expression of the RASSF10 gene induces myeloma cell proliferation due to hypermethylation of the gene promoter in multiple myeloma

“…Recent research showed that decitabine enhanced the effect of bortezomib in an MM cell line (29). Decitabine, combined with quisinostat, a histone deacetylase inhibitor, showed increased antimyeloma effects and altered immune cell constitution, such as increased dendritic cells and naive T cells, in a mouse myeloma model (30). Another study indicated that decitabine-mediated apoptosis in MM can be enhanced by combination with histone deacetylase inhibitor (31).…”

Lower expression of the RASSF10 gene induces myeloma cell proliferation due to hypermethylation of the gene promoter in multiple myeloma

“…Recent research showed that decitabine enhanced the effect of bortezomib in an MM cell line (29). Decitabine, combined with quisinostat, a histone deacetylase inhibitor, showed increased anti-myeloma effects and altered immune cell constitution, such as increased dendritic cells and naive T cells, in a mouse myeloma model (30). Another study indicated that decitabine-mediated apoptosis in MM can be enhanced by combination with histone deacetylase inhibitor (31).…”

Addition of low‐dose decitabine to bortezomib and dexamethasone as second‐line therapy in multiple myeloma

“…Hypermethylation at prognostically significant, differentially methylated regions (pd‐DMR) genes can significantly reduce the responses to anti‐myeloma therapy and perturb the interactions of the myeloma cells with the MM immune microenvironment, and demethylating agent decitabine can effectively reduce the methylation of pd‐DMR genes 9 . Furthermore, decitabine can not only synergistically enhance myeloma cell sensitivity to bortezomib, but also deplete myeloid‐derived suppressor cells (MDSCs) in the MM microenvironment, 10–12 while MDSCs are essential for myeloma cell survival and immune escape in the MM microenvironment 8 . To sum up, we believe that adding decitabine to currently available and affordable anti‐myeloma therapies would be very likely to develop novel and highly cost‐effective strategies for RRMM after first relapse.…”