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Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice.
- Source :
-
International journal of nanomedicine [Int J Nanomedicine] 2009; Vol. 4, pp. 73-8. Date of Electronic Publication: 2009 Apr 01. - Publication Year :
- 2009
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Abstract
- 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.
- Subjects :
- Animals
Antibiotics, Antineoplastic administration & dosage
Antibiotics, Antineoplastic chemistry
Benzylisoquinolines radiation effects
Daunorubicin chemistry
Drug Carriers radiation effects
Drug Resistance, Multiple
Ferric Compounds radiation effects
Humans
K562 Cells
Leukemia pathology
Mice
Mice, Nude
Nanoparticles administration & dosage
Nanoparticles radiation effects
Treatment Outcome
Apoptosis drug effects
Benzylisoquinolines chemistry
Daunorubicin administration & dosage
Drug Carriers chemistry
Ferric Compounds chemistry
Leukemia drug therapy
Nanoparticles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1178-2013
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 19421372
- Full Text :
- https://doi.org/10.2147/ijn.s5093