[The effect of selectively inhibiting the nuclear factor kappaB activation on survivin expression in leukemic cells].
OBJECTIVE
To investigate the highly specific proteasomal inhibitor MG132-induced apoptosis and its effect on nuclear factor (NF)-kappaB activation and survivin expression in leukemic K562 cell line.


METHODS
leukemic cells of the line K562 were cultured and divided into 2 groups: treatment group, undergoing co-incubation with MG132 of the concentrations of 2, 4, 6, and 8 micromol/L respectively for 24 hours, and control group without treatment of MG132. Apoptosis was detected by examination of cell morphology and flow cytometry. Survivin expression and NF-kappaB activation were analyzed by immunocytochemistry and Western blotting.


RESULTS
MG132 induced apoptosis of the K562 cells dose-dependently. Both survivin and NF-kappaB were highly expressed in the K562 cells. Compared with the control group, K562 cell treated with MG132 at the concentrations of 2, 4, 6, and 8 micromol/L for 24 hours showed the decrease of NF-kappaB activation to 75.0% +/- 3.7%, 59.9% +/- 5.3%, 45.4% +/- 5.7%, and 25.0% +/- 4.2% respectively, and decrease of survivin expression to 90.9% +/- 10.1%, 66.7% +/- 5.2%, 45.4% +/- 5.7%, and 30.3% +/- 6.6% respectively. Downregulation of survivin expression was closely correlated with the inhibition of NF-kappaB activation (Pearson correlation coefficient = 0.989, P < 0.01).


CONCLUSIONS
MG132 induces apoptosis of leukemic cells, and effectively inhibits the NF-kappaB activation accompanied by the downregulation of survivin expression.
Chen
Wei-Zhi
WZ
Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
Liu
Chuan-Fang
CF
Li
Li-Zhen
LZ
Yin
Xiao-Xiao
XX
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D020014:K562 Cells; D007976:Leupeptins / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D007976:Leupeptins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000077022:Survivin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde