Effects of different time points of bortezomib on the pathway of NF-κB in drug-resistant K562 cells / 白血病·淋巴瘤

ABSTRACT

Objective To study the effects of bortezomib on the expression of NF-κB, IκB and P-gp of drug-resistant K562 cells induced by daunorubicin (K562/DNR), to explore the molecular mechanism of drug-resistant reverse. Methods The expression of NF-κB, IκB and P-gp in K562/DNR cells were detected when the cells had been treated with 100 μg/ml DNR only or together with 4 μg/L bortezomib for 12 h, 24 h and 36 h. The apoptosis rates were detected in each group 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 increased and IκB was decreased after being treated with DNR. When K562/DNR were cultured with bortezomib, the expressions of NF-κB and P-gp induced by DNR were significantly suppressed and IκB was increased. The activity of NF-κB were detected in different time points: (15.3±1.87) %[(23.8± 2.27) % in DNR group] at 12 h, (10.2±1.69) % [(25.4±1.98) % in DNR group] at 24 h, (6.08±2.53) % [(26.9±2.58) % in DNR group] at 36 h. There were a significant differences between DNR group and DNR+PS-341group. The apoptosis rates were increased in DNR+PS-341 group at different time points than those in DNRgroup, (35.23±5.15) % [(15.56±4.12) % in DNR group] at 12 h, (40.26±6.89) % [(17.25±2.89) % in DNR group] at 24 h, (43.58±7.69) % [(22.47±4.58) % in DNR group] at 36 h. The effccts showed the character of time-dependent pattern. Conclusion Bortezomib could downregulate the expressions of NF-κB and P-gp in K562/DNR, reverse the drug resistance and up-regulate the apoptotic rates in K562/DNR cells.