Molecular mechanisms of converting K562/DNR cellular drug-resistance by bortezomib

Y.-c. Li, H.-h. Wang, A.-j. Liao, B.-b. Fu, R. Zhang, J. Li, Y. Yang, Z.-g. Liu, W. Yang

Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, China. ycchina27@163.com

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• Hematology

OBJECTIVES: The aim of this study was to observe the effects of bortezomib (PS341) on the expression of NF-κB (nuclear factor-kappa B), IκB (inhibitor kB) and P-gp (P-glycoprotein) of K562 cells induced by daunorubicin (K562/DNR).

MATERIALS AND METHODS: MTT method was used to determine the drug resistance of K562 cells and the cellular toxicity of bortezomib. Detect the expression of NF-κB, IκB and P-gp of K562/DNR 36 hours after receiving the treatment of 100 µg/ml DNR only or added with 0.4 µg/L, 4 µg/L and 40 µg/L bortezomib, and 12 hours and 24 hours after receiving the treatment of 100 µg/ml DNR only or added with 4 µg/L bortezomib by Western blot. Detect the apoptosis rate in each group by flow cytometry respectively and the activity of NF-κB was detected by ELISA method.

RESULTS: Compared with the control group, the expressions of NF-κB and P-gp in K562/DNR could be induced by DNR. When K562/DNR were cultured with bortezomib, the expressions of NF-κB and P-gp induced by DNR were significantly suppressed and this effcet increased with the increase of the concentration or the action time of bortezomib.

CONCLUSIONS: Proteasome inhibitor bortezomib could convert the cellular drug resistance to promote cell apoptosis, and this effect showed the characteristic of concentration-dependent and time-dependent pattern.

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