[Relationship between drug resistance and the expression of NF-kappaB induced in leukemic cells].
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.



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.



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.



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.
Zhang
Xiao-hong
XH
The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
Su
Li-da
LD
Lu
Qing-hua
QH
Liang
Yun
Y
Zhao
Xiao-ying
XY
D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020014:K562 Cells; D016328:NF-kappa B / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*
D001152:Arsenicals; D020672:I-kappa B Proteins; D016328:NF-kappa B; D010087:Oxides; D004317:Doxorubicin; D000077237:Arsenic Trioxide