Biomolecular mechanisms of cyclosporine A, tetrandrine and their combination on the reversion of multidrug resistance in human leukemia cell line.
- Author:
Bao-An CHEN
1
;
Jing-Jing GUO
;
Jian CHENG
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; genetics; metabolism; Benzylisoquinolines; pharmacology; Cyclosporine; pharmacology; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression; drug effects; Humans; K562 Cells; Leukemia; drug therapy; genetics; metabolism
- From: Chinese Journal of Integrated Traditional and Western Medicine 2008;28(11):1010-1013
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEMultidrug resistance (MDR) plays an important role in the failure of chemotherapy on malignant tumors. This study was to investigate the biomolecular mechanisms of cyclosporine A (CsA), tetrandrine (Tet) and their combination on multidrug resistance in cell line K562/A02.
METHODSK562/A02 cells were treated with CsA and (or) Tet. The intracellular daunorubicin (DNR) concentration and the expression of P-glycoprotein (P-gp) were observed by flow cytometry assay. The mRNA expression of mudtiding resistance gene (mdr1) was measured by fluorescent semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).
RESULTSCsA and Tet (alone or combination) elevated the intracellular DNR concentration in K562/A02 cells (the fluorescence intensity of intracellular DNR in K562/A02 cells was 60%, 65% and 98% respectively of that in K562 cells). The fluorescence intensity of P-gp in K562 and K562/A02 cells was 0.18% and 96.51%. The P-gp expression was down-regulated after treated with CsA, Tet and both (75.32%, 76.86% and 48.61%); mdr1 mRNA was also down-regulated, and the effect of their combination was more obvious.
CONCLUSIONMDR can be partially reversed by CsA or Tet, the combination of both drugs shows a great synergistic reversal effect.
