Arsenic trioxide inhibits P-glycoprotein expression in multidrug-resistant human leukemia K562/ADM cell line that overexpresses mdr-1 gene and enhances their chemotherapeutic sensitivity.
- Author:
Hu-lai WEI
1
;
Xiao-jian YAO
;
Yu-ning LI
;
Pei WANG
;
Huai-shun ZHAO
;
De-cheng BAI
;
Xiao PENG
;
Lan-fang MA
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; biosynthesis; drug effects; Antineoplastic Agents; pharmacology; Apoptosis; drug effects; Arsenicals; pharmacology; Daunorubicin; pharmacology; Doxorubicin; pharmacology; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Etoposide; pharmacology; Humans; K562 Cells; Oxides; pharmacology
- From: Chinese Journal of Hematology 2003;24(1):28-31
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of arsenic trioxide (As(2)O(3)) on the apoptosis and P-glyco-protein (P-gp) expression of multidrug-resistant human leukemia K562/ADM cells, and the combined effects of As(2)O(3) with conventional chemotherapeutic agents.
METHODSMultidrug-resistant human leukemia cell line K562/ADM that overexpresses mdr-1 gene was used as the target cells. The cell proliferating activity was assessed with a MTT assay. Cell morphology was examined by light microscopy, confocal microscopy and electron-microscopy. P-gp expression, cell-cycle status were determined by flow cytometry.
RESULTSK562/ADM cells were highly resistant to adriamycin, and cross-resistant to daunorubicin and etoposide. As(2)O(3) at concentrations of 0.5 to 20 micromol/L inhibited the proliferation of K562/ADM cells, and K562/ADM cells were more sensitive to As(2)O(3) than their parent K562 cells did. As(2)O(3) induced marked apoptosis of K562/ADM cells showed by typical apoptotic morphological changes and the appearance of high sub-G(1) cell population. As(2)O(3) significantly inhibited the P-gp expression in K562/ADM cells, and exerted a synergistic effect on the enhancement of the cell sensitivity to adriamycin, daunorubicin and etoposide.
CONCLUSIONAs(2)O(3) induces growth-inhibition and apoptosis of multidrug-resistant K562/ADM cells, and augments synergistically the sensitivity of the cells to conventional chemotherapeutic agents via down-regulation of P-gp expression.