Reversal of multi-drug resistance in K562/A02 cells by small interference RNA of mdr1 gene.
- Author:
Zhi PENG
1
;
Zhi-jian XIAO
;
Yi WANG
;
Peng LIU
;
Ying-lin CAI
;
Wen-li FENG
;
Zhong-chao HAN
Author Information
- Publication Type:Journal Article
- MeSH: Base Sequence; Daunorubicin; pharmacokinetics; Drug Resistance, Neoplasm; Genes, MDR; physiology; Humans; K562 Cells; drug effects; Molecular Sequence Data; RNA, Messenger; analysis; RNA, Small Interfering; pharmacology
- From: Chinese Journal of Hematology 2004;25(1):5-7
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of small interference RNA (siRNA) on mdr1 and P-glyco-protein (P-gp) expression of multi-drug resistance (MDR) human leukemia cell line K562/A02.
METHODSThree si RNAs (si-mdr1-1, si-mdr1-2, si-mdr1-3) which were specifically targeted mdr1 gene were synthesized and transfected into K562/A02 cells. Expression of mdr1 mRNA was assayed by RT-PCR. P-gp expression and intracellular daunorubicin (DNR) concentration were determined by flow cytometry. 50% inhibition concentration (IC(50)) of doxorubicin (ADM) on K562/A02 was determined by MTT method.
RESULTSTreatment of K562/A02 cell with the 3 kinds of siRNAs resulted in a reversal of MDR of a different extent. The third siRNA was more effective in the suppression of mdr1 with a significant reduction of (58.0 +/- 1.54)% of the mdr1 mRNA expression. Positive expression rate of p170 decreased from (76.0 +/- 1.0)% to (19.6 +/- 1.9)%, and the relative efficiency of K562/A02 to ADM was 70.4%. The intracellular accumulation of DNR increased after siRNA treatment.
CONCLUSIONThe siRNA could effectively restore the sensitivity of K562/A02 cells to conventional chemotherapeutic agents.
