Relationship between drug resistance and the expression of NF-kappaB induced in leukemic cells / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To explore the relationship between drug resistance of leukemic cells and the expression of both IkappaB-alpha and NF-kappaB associated with apoptosis induced by arsenic trioxide (As2O3) in K562 and K562/ADR cells.</p><p><b>METHODS</b>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-kappaB in nuclear and IkappaB-alpha in cytoplasm of these cells. Apoptosis and degradation of IkappaB-alpha protein were also observed by flow cytometry.</p><p><b>RESULTS</b>After exposure to As2O3, the ratio of apoptosis cells in K562/ADR was significantly lower than that in K562 cells. K562/ADR [(6.33+/-1.51)%] and K562 cells [(13.25+/-1.83)%] cultured with 1 micromol/L As2O3 were in apoptosis. When cultured with 4 micromol/L As2O3, the apoptosis cells increased to (8.00+/-1.47)% and (50.56+/-8.62)%, respectively. The level of IkappaB-alpha in K562 cytoplasm was down-regulated from 88.07% to 49.21% after As2O3 stimulation, while NF-kappaB in nuclear was up-regulated, that was not found in K562/ADR cells.</p><p><b>CONCLUSION</b>As2O3 could induce apoptosis of K562 cells, associated with the degradation of IkappaB-alpha and the activation of NF-kappaB. There are an elevated expression of NF-kappaB and resistance to apoptosis induced by As2O3 in K562/ADR cells.</p>