Reversal of P-glycoprotein-dependent resistance to adriamycin by 5-bromotetrandrine in K562/A02 cell line

Chen, B.; Wang, J.; Gao, Chen; Ding, Jingjin; Yalan, Sun; Gao, Feng; Cheng, Jian; Zhao, Guozhi; Chen, N.

doi:10.1200/jco.2008.26.15_suppl.13557

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“…Notably, BrTet, an excellent reversal of P-gp mediated MDR, 23,26 significantly enhanced the anticancer activity of doxorubicin in vitro by inhibiting the overexpression of P-gp. 27 To overcome drug resistance and reduce the side effects during chemotherapy, nanotechnology holds promising potential, utilizing targeted drug delivery. In this study, the ability of a novel chemotherapy formulation (DNR/BrTetMNPs) to overcome P-gp-mediated drug resistance in K562/ A02 cells was investigated, and the efficacy evaluated.…”

Section: Discussionmentioning

confidence: 99%

A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

Chen¹

2011

IJN

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Abstract:To overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from multidrug resistance (MDR) and minimize adverse effects of chemotherapy agents, a novel chemotherapy formulation of magnetic nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin (DNR/BrTet-MNPs) was developed, and its effect on MDR leukemic cells was explored. After the DNR and Br were co-loaded onto a pluronic-stabilized and oleic acid-modified magnetic nanosystem, the physical characteristic and drug-loading capacity were evaluated. The cell toxicity of the self-prepared DNR/BrTet-MNPs formulation was then determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay; the cellular uptake of drug was demonstrated by fluorescent microscope. Lastly, the transcription of mdr1 and the expression of P-glycoprotein (P-gp) were detected by the reverse transcription reaction and western blotting assay, respectively. The results showed that the selfprepared DNR/BrTet-MNPs formulation possessed a sustained release of drug and displayed a dose-dependent antiproliferative activity on MDR leukemia K562/A02 cells. It also enhanced the accumulation of intracellular DNR in K562/A02 cells and downregulated the transcription of the mdr1 gene and the expression of P-gp. These findings suggest that the remarkable effect of the novel DNR/BrTet-MNPs formulation, acting as a drug depot system for the sustained release of the loaded DNR and BrTet, on multidrug resistance leukemia K562/A02 cells would be a promising strategy for overcoming MDR.

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Section: Discussionmentioning

confidence: 99%

A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

Chen¹

2011

IJN

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Reversal of P-glycoprotein-dependent resistance to adriamycin by 5-bromotetrandrine in K562/A02 cell line

Cited by 1 publication

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A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

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