Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells.
This study aims to evaluate the multidrug resistance (MDR) reversal activity by magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) and 5-bromotetrandrine (BrTet) MDR cell line K562/A02 solitarily or symphysially. The proliferation of K562 and K562/A02 cells and the cytotoxicity on peripheral blood mononuclear cells (PMBCs) were evaluated by MTT assay. Cellular accumulation of daunorubicin (DNR) was analyzed by flow cytometry. Real-time polymerase chain reaction and Western blotting analyses were performed to examine the mRNA and protein levels of mdr1, respectively. The results showed that the combination of MNPs-Fe3O4 and BrTet with effective concentrations significantly increased cytotoxicity against MDR cell line K562/A02. Both BrTet and MNPs-Fe3O4 increased the intracellular DNR accumulation in the K562/A02 cell line, and downregulated the level of mdr1 gene and expression of P-glycoprotein. Furthermore, the combination did not have significant cytotoxicity in PMBCs. We propose that MNPs-Fe3O4 conjugated with DNR and BrTet probably have synergetic effects on MDR reversal.
Cheng
Jian
J
Department of Hematology, The Affiliated Zhongda Hospital, Southeast University, Nanjing 210009, People's Republic of China.
Wu
Weiwei
W
Chen
Bao-an
BA
Gao
Feng
F
Xu
Wenlin
W
Gao
Chong
C
Ding
Jiahua
J
Sun
Yunyu
Y
Song
Huihui
H
Bao
Wen
W
Sun
Xinchen
X
Xu
Cuirong
C
Chen
Wenji
W
Chen
Ningna
N
Liu
Lijie
L
Xia
Guohua
G
Li
Xiaomao
X
Wang
Xuemei
X
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D001483:Base Sequence; D044182:Benzylisoquinolines / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D015536:Down-Regulation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D019450:Genes, MDR / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008280:Magnetics; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D050997:Nanomedicine; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D044182:Benzylisoquinolines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C514835:bromotetrandrine; D052203:Ferrosoferric Oxide; D003630:Daunorubicin