[Study on the relationship of beta-catenin level and sensitivity to Bortezomib of myeloma cell lines].
OBJECTIVE
To explore the relationship of beta-catenin and sensitivity to Bortezomib of myeloma cell lines.


METHODS
Myeloma cell lines RPMI8226, CZ-1 and NCI-H929 were treated with Bortezomib and 2ME2, alone or in combination. Typan blue dye exclusion and modified MTT were used to assess the cell viability with or without treatment. Annexin V-FITC and PI staining was performed to detect apoptosis rate. RT-PCR was used to detect beta-catenin mRNA and western blot to analyze beta-catenin protein.


RESULTS
The basic expression level of beta-catenin was different in tested myeloma cell lines: RPMI8226 was the most while NCI-H929 the least and CZ-1 the intermediate. IC50 of RPMI8226, CZ-1 and NCI-H929 were (49.8 +/- 0.6), (24.7 +/- 0.4) and (8.4 +/- 0.2) nmol/L, respectively. After the treatment of Bortezomib (at 0, 1, 5, 10 nmol/L), beta-catenin level of tested cell lines accumulated in a time and dose dependent manner for western blot, while no significant change was observed in the result of RT-PCR. The beta-catenin protein levels in the Bortezomib (5 nmol/L) and 2ME2 (1 micromol/L) treated cell group were much lower than that in Bortezomib (5 nmol/L) group, the decrease of the gray scale of beta-catenin/beta-actin was 64.03% for RPMI8226, 52.56% for CZ-1, 51.48% for NCI-H929, and the apoptosis rates were 8.00, 1.86 and 1.19 times increase compared to untreated group.


CONCLUSIONS
Myeloma cell lines with higher beta-catenin level are less sensitive to Bortezomib, and combination treatment of low dose 2ME2 and Bortezomib can reduce beta-catenin accumulation and enhance the sensitivity to Bortezomib.
Zhou
Li-Li
LL
Department of Hematology, Shanghai Changzheng Hospital, Shanghai 200003, China.
Fu
Wei-Jun
WJ
Yuan
Zhen-Gang
ZG
Wang
Dong-Xing
DX
Hou
Jian
J
D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D001897:Boronic Acids; D011719:Pyrazines; D012333:RNA, Messenger; D051176:beta Catenin; D000069286:Bortezomib