Li Y-C, Wang H-H, Liao A-J, Fu B-B, Zhang R, Li J, Yang Y, Liu Z-G, Yang W
Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, China.
Eur Rev Med Pharmacol Sci. 2014;18(10):1465-72.
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).
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.
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.
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.
本研究旨在观察硼替佐米（PS341）对柔红霉素诱导的K562细胞（K562/DNR）中核因子-κB（NF-κB）、κB抑制蛋白（IκB）和P-糖蛋白（P-gp）表达的影响。
采用MTT法测定K562细胞的耐药性及硼替佐米的细胞毒性。仅用100μg/ml柔红霉素处理或分别添加0.4μg/L、4μg/L和40μg/L硼替佐米处理后36小时，以及仅用100μg/ml柔红霉素处理或添加4μg/L硼替佐米处理后12小时和24小时，通过蛋白质免疫印迹法检测K562/DNR中NF-κB、IκB和P-gp的表达。分别采用流式细胞术检测各组细胞凋亡率，并用ELISA法检测NF-κB的活性。
与对照组相比，柔红霉素可诱导K562/DNR中NF-κB和P-gp的表达。当K562/DNR与硼替佐米共同培养时，柔红霉素诱导的NF-κB和P-gp的表达受到显著抑制，且这种抑制作用随硼替佐米浓度的增加或作用时间的延长而增强。
蛋白酶体抑制剂硼替佐米可逆转细胞耐药性，促进细胞凋亡，且该作用呈浓度和时间依赖性。
