Cyclosporine diminishes multidrug resistance in K562/ADM cells and improves complete remission in patients with acute myeloid leukemia.
This study was designed to investigate the effects of cyclosporine A (CsA) on a multidrug resistance cultured cell line, and its effect on complete remission in patients with acute myeloid leukemia (AML). A multidrug resistant K562/ADM cell line and drug-sensitive K562 cell line was used. The intracellular concentration of daunorubicin and the accumulation of Rhodamine 123 (Rh123) in the K562/ADM and K562 cells were evaluated. Clinical effects of CsA were also studied in 65 patients with AML. In the K562/ADM cells, the 50% of inhibition concentration (IC50) of daunorubicin only group was 23.0+/-5.2 micromol/L, which was greater than in other groups co-administered with CsA (1.2+/-4.8 micromol/L), verapamil (1.5+/-5.4 micromol/L) or CsA+verapamil (1.4+/-4.3 micromol/L) (all P<0.01). The relative fluorescence intensity of Rh123 in the K562/ADM cells treated with CsA and daunorubicin was increased from 48.9% to 69.8% (P<0.05). CsA also improved the complete remission rate in the AML patients (72.7% vs 21.9%, P<0.01). We conclude that CsA can significantly diminish the multidrug resistance in K562/ADM cells. It also enhances the complete remission rates in patients with AML. CsA may be used as an integral part of the chemotherapy for AML.
Li
Guang-Yao
GY
Division of Hematology, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province 252000, PR China.
Liu
Ji-Zhu
JZ
Zhang
Bin
B
Wang
Le-Xin
LX
Wang
Chun-Bo
CB
Chen
Shou-Guo
SG
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000627:therapeutic use*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020112:Rhodamine 123 / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014700:Verapamil / Q000008:administration & dosage
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D005456:Fluorescent Dyes; D003561:Cytarabine; D020112:Rhodamine 123; D016572:Cyclosporine; D014700:Verapamil; D015255:Idarubicin; D003630:Daunorubicin