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 fac - tor-kappa B), I κB (inhibitor kB) and P-gp (P-gly - coprotein) of K562 cells induced by daunoru - bicin (K562/DNR). MATERIALS AND METHODS: MTT method was used to determine the drug resistance of K562 cells and the cellular toxicity of borte - zomib. Detect the expression of NF- κB, I κB 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 apopto - sis rate in each group by flow cytometry respec - tively 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 in - crease of the concentration or the action time of bortezomib. CONCLUSIONS: Proteasome inhibitor borte - zomib could convert the cellular drug resistance to promote cell apoptosis, and this effect showed the characteristic of concentration-de - pendent and time-dependent pattern.