Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice.
In this paper we establish the xenograft leukemia model with stable multidrug resistance in nude mice and to investigate the reversal effect of 5-bromotetrandrine (5-BrTet) and magnetic nanoparticle of Fe(3)O(4) (MNP-Fe(3)O(4)) combined with daunorubicin (DNR) in vivo. Two subclones of K562 and K562/A02 cells were inoculated subcutaneously into the back of athymic nude mice (1 x 10(7) cells/each) respectively to establish leukemia xenograft models. Drug-resistant and sensitive tumor-bearing nude mice were assigned randomly into five groups which were treated with normal saline; DNR; NP-Fe(3)O(4) combined with DNR; 5-BrTet combined with DNR; 5-BrTet and MNP-Fe(3)O(4) combined with DNR, respectively. The incidence of formation, growth characteristics, weight, and volume of tumors were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of Bcl-2, and BAX were detected by Western blot. Bcl-2, BAX, and caspase-3 genes were also detected. For K562/A02 cells xenograft tumors, 5-BrTet and MNP-Fe(3)O(4) combined with DNR significantly suppressed growth of tumor. A histopathologic examination of tumors clearly showed necrosis of the tumors. Application of 5-BrTet and MNP-Fe(3)O(4) inhibited the expression of Bcl-2 protein and upregulated the expression of BAX and caspase-3 proteins in K562/A02 cells xenograft tumor. It is concluded that 5-BrTet and MNP-Fe(3)O(4) combined with DNR had a significant tumor-suppressing effect on a MDR leukemia cells xenograft model.
Chen
Baoan
B
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, 210009, PR China.
Cheng
Jian
J
Wu
Yanan
Y
Gao
Feng
F
Xu
Wenlin
W
Shen
Huilin
H
Ding
Jiahua
J
Gao
Chong
C
Sun
Qian
Q
Sun
Xinchen
X
Cheng
Hongyan
H
Li
Guohong
G
Chen
Wenji
W
Chen
Ningna
N
Liu
Lijie
L
Li
Xiaomao
X
Wang
Xuemei
X
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000737:chemistry* / Q000528:radiation effects; D003630:Daunorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000528:radiation effects; D018432:Drug Resistance, Multiple; D005290:Ferric Compounds / Q000737:chemistry* / Q000528:radiation effects; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D044182:Benzylisoquinolines; D004337:Drug Carriers; D005290:Ferric Compounds; C514835:bromotetrandrine; C000499:ferric oxide; D003630:Daunorubicin