[Biomolecular mechanisms of cyclosporine A, tetrandrine and their combination on the reversion of multidrug resistance in human leukemia cell line].
OBJECTIVE
Multidrug 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.


METHODS
K562/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).


RESULTS
CsA 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.


CONCLUSIONS
MDR can be partially reversed by CsA or Tet, the combination of both drugs shows a great synergistic reversal effect.
Chen
Bao-An
BA
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing. cba8888@hotmail.com
Guo
Jing-Jing
JJ
Cheng
Jian
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044182:Benzylisoquinolines; C009438:tetrandrine; D016572:Cyclosporine