[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].

Article Details

Citation

Wei HL, Yao XJ, Li YN, Wang P, Zhao HS, Bai DC, Peng X, Ma LF

[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].

Zhonghua Xue Ye Xue Za Zhi. 2003 Jan;24(1):28-31.

PubMed ID
12679007 [ View in PubMed
]
Abstract

OBJECTIVE: To 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. METHODS: Multidrug-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. RESULTS: K562/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. CONCLUSION: As(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.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
Arsenic trioxideP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
Pharmaco-transcriptomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
Arsenic trioxideApproved InvestigationalCDKN2B1030
upregulated
arsenic trioxide results in increased expression of CDKN2B mRNA9p21.3
Arsenic trioxideApproved InvestigationalDNMT3A1788
downregulated
arsenic trioxide results in decreased expression of DNMT3A mRNA2p23.3
Arsenic trioxideApproved InvestigationalDNMT3B1789
downregulated
arsenic trioxide results in decreased expression of DNMT3B mRNA20q11.21