@Article{096504018X15443011011637,
AUTHOR = {Yulong Jin, Li Xu, Xiaodong Wu, Juan Feng, Mimi Shu, Hongtao Gu, Guangxun Gao, 
Jinyi Zhang, Baoxia Dong, Xiequn Chen},
TITLE = {Synergistic Efficacy of the Demethylation Agent Decitabine in Combination  With the Protease Inhibitor Bortezomib for Treating Multiple Myeloma  Through the Wnt/b-Catenin Pathway},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {6},
PAGES = {729--737},
URL = {http://www.techscience.com/or/v27n6/48589},
ISSN = {1555-3906},
ABSTRACT = {Multiple myeloma (MM) is a hematopoietic malignancy characterized by the clonal proliferation of antibodysecreting plasma cells. Bortezomib (BZM), the first FDA-approved proteasome inhibitor, has significant 
antimyeloma activity and prolongs the median survival of MM patients. However, MM remains incurable 
predominantly due to acquired drug resistance and disease relapse. -Catenin, a key effector protein in 
the canonical Wnt signaling pathway, has been implicated in regulating myeloma cell sensitivity to BZM. 
Decitabine (DAC) is an epigenetic modulating agent that induces tumor suppressor gene reexpression based 
on its gene-specific DNA hypomethylation. DAC has been implicated in modulating Wnt/ -catenin signaling 
by promoting the demethylation of the Wnt/ -catenin antagonists sFRP and DKK. In this study, we report the 
effects of single reagent DAC therapy and DAC combined with BZM on -catenin accumulation, myeloma 
cell survival, apoptosis, and treatment sensitivity. Our study proved that DAC demethylated and induced the 
reexpression of the Wnt antagonists sFRP3 and DKK1. DAC also reduced GSK3 (Ser9) phosphorylation 
and decreased -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 BZM-induced 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/ -catenin signaling. Our results can be used to optimize therapeutic regimens for MM.},
DOI = {10.3727/096504018X15443011011637}
}