Relationship between drug resistance and the expression of NF-kappaB induced in leukemic cells.
- Author:
Xiao-hong ZHANG
1
;
Li-da SU
;
Qing-hua LU
;
Yun LIANG
;
Xiao-ying ZHAO
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Arsenicals; pharmacology; Doxorubicin; pharmacology; Drug Resistance, Neoplasm; Gene Expression Regulation, Leukemic; drug effects; Humans; I-kappa B Proteins; metabolism; K562 Cells; NF-kappa B; metabolism; Oxides; pharmacology
- From: Journal of Zhejiang University. Medical sciences 2004;33(5):421-426
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSApoptosis 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.
RESULTSAfter 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.
CONCLUSIONAs2O3 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.
