Synergistic efficacy of the demethylation agent decitabine in combination with the protease inhibitor bortezomib for treating multiple myeloma through the Wnt/ βcatenin pathway.

In this study, we report the effects of single reagent DAC therapy and DAC combined with BZM on β-catenin accumulation, myeloma cell survival, apoptosis and treatment sensitivity. Our study proved that DAC demethylated and induced the re-expression of the Wnt antagonists sFRP3 and DKK1. DAC also reduced GSK3β (Ser9) phosphorylation and decreased β-catenin accumulation in the nucleus, which were induced by BZM. Thus, the transcription of cyclin D1, c-Myc and LEF/TCF was reduced, which synergistically inhibited cell proliferation, enhanced BZM-induced apoptosis, and promoted BZMinduced cell cycle arrest in myeloma cells. In summary, these results indicated that DAC could synergistically enhance myeloma cell sensitivity to BZM at least partly by regulating Wnt/β-catenin signaling. Our results can be used to optimize therapeutic regimens for MM. PMID: 30837032 [PubMed - as supplied by publisher]
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research