Effects of different concentrations of bortezomib on the expression of NF-κB, IκB and P-gp of DNR-resistant K562 cells
AIM: To observe the effects of bortezomib (PS-341) on the expression of NF-κB, IκB and P-gp of K562 cells inducedby daunorubicin (K562/DNR). METHODS: MTr method was used to determine the drug-resistant K562 cells and the cellular toxicity of bortezomib; Detect the expression of NF-κB, IκB and P-gp of K562/DNR 36 h after receiving the treatment of 100 mg/L DNR only or added with 0.4,4 and 40 gμ/L bortezomib. Detect the apoptosis rate 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 group could be induced by DNR. When K562/DNR cells were cultured with bortezomib,the expressions of NF-κB and P-gp induced by DNR were significantly suppressed and IκB was increased, these effects increased with the increase of the concentration of PS-341. The results of NF-κB's activity showed that the team of DNR was 25.9±2.5, DNR + 0.4 μg/L PS-341 was 20.3 ±2.0,DNR +4 μL PS-341was 6.1+2.5,DNR +40 μg/L PS-341 was 4.6±1.6. The activity of NF-κB was suppressed when PS-341 was added in. The results of apaptosis rate (%) showed that the team of DNR was 22.5±4.6, DNR + 0.4 μg/L PS-341 was 31.0 ± 5.2,DNR +4 μg/L PS-341was 43.6±7.7, DNR +40 μg/L PS-341 was 56.0 ± 9.3. The apoptosis rate in-creased when K562/DNR cells were cultured with bortezomib, these effects increased with the increase of concentration of bortezomih. CONCLUSION: Bortezomib ceuld convert the cellulardrug resistance and this effect showed the characteristic of concentration-dependent pattern.
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