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[The effect of selectively inhibiting the nuclear factor kappaB activation on survivin expression in leukemic cells]
Wei-Zhi Chen1, Chuan-Fang Liu, Li-Zhen Li
1Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
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).
Conclusion:
MG132 induces apoptosis of leukemic cells, and effectively inhibits the NF-kappaB activation accompanied by the downregulation of survivin expression.
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