title: Reversal of multidrug resistance in xenograft nude-mice by magnetic Fe(3)O(4) nanoparticles combined with daunorubicin and 5-bromotetrandrine.
abstract: 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.
authors.affiliation: Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical School, Nanjing 210009, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wu
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Xu
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Chong
authors.initials: C
authors.lastname: Gao
authors.forename: Xin-Chen
authors.initials: XC
authors.lastname: Sun
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Li
authors.forename: Wen-Ji
authors.initials: WJ
authors.lastname: Chen
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Liu
authors.forename: Xiao-Mao
authors.initials: XM
authors.lastname: Li
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Wang
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D005290:Ferric Compounds; C514835:bromotetrandrine; D003630:Daunorubicin