Relationship between the As₂O₃ Induced Expression of NF-κB and Drug Resistance in K562/ADR Cells.

Summery: Anti-apoptosis is one of drug resistance mechanisms in leukemic cells. It was found in our early study that As₂O₃ can induce apoptosis of K562 cells, and this effect involve the degradation of IκB-αand consequently the activation of NF-κB. The relationship between drug resistance of leukemic cells and the expression of both IκB-αand NF-κB associated with apoptosis induced by arsenic trioxide(As₂O₃) was studied in K562 and K562/ADR cells.

Methods: Apoptosis was induced in K562 and K562/ADR cells cultured with As₂O₃ in different concentrations. Western blot was used to analyze the expression of NF-κB in nuclear and IκB-α in cytoplasm of these cells. Apoptosis and degradation of IκB-αprotein were also observed by flow cytometry.

Results: The suppressive effect of As₂O₃ on proliferation of K562/ADR was lower than that in K562 cell, IC50 values were 19.07μmol/L and 5.26μmol/L, respectively. After exposure to As₂O₃, the ratio of apoptosis cells increased with the concentration of As₂O₃ in K562 cells, from(13.25±1.83)% to (50.56±8.62)% with variation of As₂O₃ from 1μmol/L to 4μmol/L(P<0.05). The ratio of apoptosis cells in K562/ADR cultured with 4μmol/L As₂O₃ was significantly lower than that in K562 cells, (8.00±1.47)% vs. (50.56±8.62)%, (P<0.05). The level of IκB-α in K562 cytoplasm was down-regulated from (88.07±0.99)% to (49.21±0.95)%, (P<0.01) after As₂O₃ stimulation, while NF-κB in nuclear was up-regulated, that was not found in K562/ADR cells.

Conclusion: As₂O₃ could induce apoptosis of K562 cells, associated with the degradation of IκB-αand the activation of NF-κB. There were resistance to As₂O₃ induced apoptosis and an abnormal regulation of NF-κB expression by As₂O₃ in K562/ADR cells.