Arsenic trioxide and 2-methoxyestradiol reduce beta-catenin accumulation after proteasome inhibition and enhance the sensitivity of myeloma cells to Bortezomib.
Beta-catenin, the key protein in canonical Wingless/int (Wnt) pathway, degrades via ubiquitin-proteasome pathway. Recently, it proved important roles in the proliferation of myeloma cells. But little is known about whether cytoplasmic beta-catenin content is associated with myeloma cell's sensitivity to Bortezomib. We examined the constitutive expression of beta-catenin in five myeloma cell lines and primary cells from patients. Meanwhile, the effect of Bortezomib combined with arsenic trioxide (As(2)O(3))/2-methoxyestradiol (2ME2) on beta-catenin accumulation, myeloma cells' survival, apoptosis and their sensitivity to Bortezomib were also investigated. Our study proved that beta-catenin protein levels are negatively associated with myeloma cells' sensitivity to Bortezomib. As(2)O(3)/2ME2 can reduce cytoplasmic beta-catenin accumulation after proteasome inhibition and enhance myeloma cells' sensitivity to Bortezomib. This will preliminarily help to optimize the new therapeutic regimens for MM treatment in the future.
Zhou
Lili
L
Department of Hematology, the Second Affiliated Hospital to the Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
Hou
Jian
J
Fu
Weijun
W
Wang
Dongxing
D
Yuan
Zhenggang
Z
Jiang
Hua
H
D000077584:2-Methoxyestradiol; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D015153:Blotting, Western; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D049109:Cell Proliferation / Q000187:drug effects; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000008:administration & dosage; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics*
D001152:Arsenicals; D001897:Boronic Acids; C495270:CTNNB1 protein, human; D010087:Oxides; D061988:Proteasome Inhibitors; D011719:Pyrazines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051176:beta Catenin; D004958:Estradiol; D000069286:Bortezomib; D000077584:2-Methoxyestradiol; D000077237:Arsenic Trioxide