[Reversal of multi-drug resistance in K562/A02 cells by small interference RNA of mdr1 gene].
OBJECTIVE
To 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.


METHODS
Three 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.


RESULTS
Treatment 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.


CONCLUSIONS
The siRNA could effectively restore the sensitivity of K562/A02 cells to conventional chemotherapeutic agents.
State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS & PUMC, Tianjin 300020, China.
Zhi
Z
Peng
Zhi-jian
ZJ
Xiao
Yi
Y
Wang
Peng
P
Liu
Ying-lin
YL
Cai
Wen-li
WL
Feng
Zhong-chao
ZC
Han
D001483:Base Sequence; D003630:Daunorubicin / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D019450:Genes, MDR / Q000502:physiology*; D006801:Humans; D020014:K562 Cells / Q000187:drug effects*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003630:Daunorubicin