@article{CJCR895,
author = {Hui-han Wang and Ying-chun Li and Ai-jun Liao and Bei-bei Fu and Wei Yang and Zhuo-gang Liu and Xiao-bin Wang},
title = {Reversion of Multidrug-Resistance by Proteasome Inhibitor Bortezomib in K562/DNR Cell Line},
journal = {Chinese Journal of Cancer Research},
volume = {23},
number = {1},
year = {2012},
keywords = {},
abstract = {Objective: To observe the reversion of multi-drug resistance by proteasome inhibitor bortezomib in K562/DNR cell line and to analyze the possible mechanism of reversion of multidrug-resistance.
Methods: MTT method was used to determine the drug resistance of K562/DNR cells and the cellular toxicity of bortezomib. K562/DNR cells were cultured for 12 hours, 24 hours and 36 hours with 100 μg/ml DNR only or plus 4 μg/L bortezomib. The expressions of NF-κB, IκB and P-gp of K562/DNR were detected with Western blot method, the activity of NF-κB was tested by ELISA method and the apoptosis rate was observed in each group respectively.
Results: The IC50 of DNR on cells of K562/S and K562/DNR groups were 1.16 μg/ml and 50.43 μg/mL, respectively. The drug-resistant fold was 43.47. The IC10 of PS-341 on Cell strain K562/DNR was 4 μg/L. Therefore, 4 μg/L was selected as the concentration for PS-341 to reverse drug-resistance in this study. DNR induced down-regulation of IκB expression, up-regulation of NF-κB and P-gp expression. After treatment with PS-341, a proteasome inhibitor, the IκB degradation was inhibited, IκB expression increased, NF-κB and P-gp expression decreased in a time dependent manner. Compared to DNR group, the NF-κB p65 activity of DNR+PS-341 group was decreased. Compared to corresponding DNR group, DNR induced apoptosis rate increases after addition of PS-341 in a time dependent manner.
Conclusion: Proteasome inhibitor bortezomib can convert the leukemia cell drug resistance. The mechanism may be that bortezomib decreases the degradation of IκB and the expression of NF-κB and P-gp, therefore induces the apoptosis of multi-drug resistant cells.},
issn = {1993-0631}, url = {https://cjcr.amegroups.org/article/view/895}
}