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-kappa B (nuclear factor-kappa B), I kappa B (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-kappa B, I kappa B and P-gp of K562/DNR 36 hours after receiving the treatment of 100 mu g/ml DNR only or added with 0.4 mu g/L, 4 mu g/L and 40 mu g/L bortezomib, and 12 hours and 24 hours after receiving the treatment of 100 mu g/ml DNR only or added with 4 mu g/L bortezomib by Western blot. Detect the apoptosis rate in each group by flow cytometry respectively and the activity of NF-kappa B was detected by ELISA method. RESULTS: Compared with the control group, the expressions of NF-kappa B and P-gp in K562/DNR could be induced by DNR. When K562/DNR were cultured with bortezomib, the expressions of NF-kappa B 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.