[Effects of cytokines on multidrug-resistance in K562/A02 cells].
OBJECTIVE
To explore the effects of cytokines on human leukemic cell line K562/S and its multidrug-resistant counterpart K562/A02.


METHODS
The toxicities of cytokines and the IC50 (the concentration causing 50% inhibition of cell growth) of DNR were assayed by MTT method; intracellular drug concentration was measured by fluorometry; p-glycoprotein (p-gp) expression was detected by APAAP and mdr-1 mRNA was assayed by RT-PCR.


RESULTS
The IC50 of DNR for K562/A02 and K562/S cells were 45.08 microg/ml and 0.607 microg/ml, respectively. Pretreating K562/A02 cells with rhu IFN (500 U/ml) or rhu IL-2 (250 U/ml) for 24 hours partially restored the sensitivity of K562/A02 cells to DNR (IC50 were 16.39 and 11.96 microg/ml, respectively) but had not effect on K562/S cells, and it elevated the intracellular DNR accumulation in K562/A02 from 2151 ng/mg x protein to 2570 and 2503ng/mg x protein, respectively. p-gp and mdr-1 mRNA were not down regulated. By contrast, rhu G-CSF and rhu GM-CSF had no effect on either K562/A02 or K562/S.


CONCLUSIONS
rhu IFN or rhu IL-2 could partially restore the sensitivity of K562/A02 to DNR and elevate the intracellular DNR accumulation via a mechanism independent of p-gp or mdr-1 mRNA down-regulation.
Liu
L
L
Department of Hematology, TongRen Hospital, Beijing 100730
Liu
F
F
Yang
C
C
Qi
Y
Y
Yang
L
L
Qi
J
J
Xu
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D020014:K562 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016207:Cytokines; D012333:RNA, Messenger; D004317:Doxorubicin