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

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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