[In vitro reversal effect of cyclosporin A in combination with cytokines on multidrug resistant cell line K562/A02].
OBJECTIVE
To explore the reversal effect of cyclosporin A(CsA) in combination with cytokines on multidrug resistant cell line K562/A02.


METHODS
The cytotoxicities of daunorubicin(DNR) were assayed by MTT method. Intracellular rhodamine(Rh123) concentration was measured by flow cytometry. P-glycoprotein(p-gp) expression was analyzed for staining with monoclonal JSB-1. Mdr1 mRNA expression was detected by RT-PCR.


RESULTS
The cytotoxicities of DNR to K562/A02 were enhanced by 1 mumol/L CsA, 500 U/ml IFN-alpha and 200 U/ml, IL-2 respectively, and their IC50 was (3.78 +/- 0.03), (13.77 +/- 0.38) mu/ml, (18.5 +/- 0.60) micrograms/ml. Their reversal effect was 6.70, 1.84 and 1.37 times than that of K562/A02. But IC50 of combined CsA and IFN-alpha was (1.71 +/- 0.19) micrograms/ml; its reverse effect increased in 14.8 times. The combination could increase intracellular Rh123 accumulation significantly as compared with either of them alone, but p-gp and mdr1 mRNA expression were not decreased obviously. CsA in combination with IL-2 didn't show a synergistic effect.


CONCLUSIONS
Mdr could be partially reversed by cytokines or low doses CsA(1 mumol/L), but the combination of CsA and IFN-alpha showed a greater synergistic reversal interaction.
Pu
J
J
Department of Hematology, Chinese PLA General Hospital, Beijing 100853.
Lou
F
F
Zhou
Q
Q
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D020014:K562 Cells / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016207:Cytokines; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D016572:Cyclosporine; D003630:Daunorubicin