Reversal of multidrug resistance in xenograft nude-mice by magnetic Fe(3)O(4) nanoparticles combined with daunorubicin and 5-bromotetrandrine.
This study was aimed to investigate the reversal effect of 5-bromotetrandrine (5-BrTet) and magnetic nanoparticle of Fe(3)O(4) (Fe(3)O(4)-MNPs) combined with DNR in vivo. The xenograft leukemia model with stable multiple drug resistance in nude mice was established. The two sub-clones of K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1 x 10(7) cells/each) to establish the leukemia xenograft models. Drug resistant and the sensitive tumor-bearing nude mice were both assigned randomly into 5 groups: group A was treated with NS; group B was treated with DNR; group C was treated with nanoparticle of Fe(3)O(4) combined with DNR; group D was treated with 5-BrTet combined with DNR; group E was treated with 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were carried out. The protein levels of BCL-2, BAX, and Caspase-3 in resistant tumors were detected by Western blot. The results indicated that 5-BrTet and magnetic nanoparticle of Fe(3)O(4) combined with DNR significantly suppressed growth of K562/A02 cell xenograft tumor, histopathologic examination of tumors showed the tumors necrosis obviously. Application of 5-BrTet and magnetic nanoparticle of Fe(3)O(4) inhibited the expression of BCL-2 protein and up-regulated the expression of BAX, and Caspase-3 protein in K562/A02 cell xenograft tumor. It is concluded that 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR have significant tumor-suppressing effect on MDR leukemia cell xenograft model.
Wu
Ya-Nan
YN
Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical School, Nanjing 210009, China.
Chen
Bao-An
BA
Cheng
Jian
J
Gao
Feng
F
Xu
Wen-Lin
WL
Ding
Jia-Hua
JH
Gao
Chong
C
Sun
Xin-Chen
XC
Li
Guo-Hong
GH
Chen
Wen-Ji
WJ
Liu
Li-Jie
LJ
Li
Xiao-Mao
XM
Wang
Xue-Mei
XM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D005290:Ferric Compounds; C514835:bromotetrandrine; D003630:Daunorubicin