| Título: | Reversion of Multidrug-Resistance by Proteasome Inhibitor Bortezomib in K562/DNR Cell Line |
| Autores: |
Wang, Hui-han Li, Ying-chun Liao, Ai-jun Fu, Bei-bei Yang, Wei Liu, Zhuo-gang Wang, Xiao-bin |
| Fecha: | 2011-03-30 |
| Publicador: | Chinese Journal of Cancer Research |
| Fuente: |
Ver documento |
| Tipo: | |
| Tema: | No aplica |
| Descripción: | 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. |
| Idioma: | Inglés |