[Effect of cyclosporine A, raloxifene and their combination on the reversion of multidrug resistance of K562/A02 line].
This study was aimed to investigate the reversible effect of cyclosporine A, raloxifene and their combination on multidrug resistance cell line K562/A02. The IC(50) (the concentration causing 50% inhibition of cell growth) of DNR were assayed by MTT method, the expression level of mdr-1 mRNA was assayed by RT-PCR, p-glycoprotein (P-gp) expression and intracellular DNR concentration were detected by flow cytometry. The results showed that the IC(50) of DNR on K562/A02 and K562 cells were 23.51 mg/L and 0.29 mg/L, respectively. The IC(50) of DNR on K562/A02 cells in treatment with raloxifene CsA and both combination were 5.98, 8.15 and 3.68 mg/L respectively, but both drugs not influenced IC(50) of DNR on K562 cells. Pretreating K562/A02 cells with raloxifene (2.5 mg/L) or CsA (1 mg/L) for 48 hours partially restored the sensitivity of K562/A02 cells to DNR. Cyclosporine A and raloxifene (alone or combination) elevated the intracellular DNR concentration in K562/A02, down regulated P-gp and mdr-1 mRNA expressions. It is concluded that multidrug resistance (MDR) can be partially reversed by CsA or raloxifene, the combination of both drugs shows a great synergistic reversal effect.
Bao
Wen
W
Department of Hematology, Zhongda Hospital, Clinical medical college of Southeast University, Nanjing 210009, China.
Chen
Bao-An
BA
Gao
Feng
F
Ding
Jia-Hua
JH
Xu
Wen-Lin
WL
Sheng
Hui-Ling
HL
Gao
Chong
C
Sun
Yun-Yu
YY
Chen
Jian
J
Wang
Jun
J
Zhao
Gang
G
Ma
Yan
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D020014:K562 Cells / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D020849:Raloxifene Hydrochloride; D004317:Doxorubicin; D016572:Cyclosporine