Modulation of multidrug resistance in human leukemia cells with mdr1-targeted antisense oligonucleotides using variable treatment schedules

Dassow, Hannelore; Laßner, Dirk; Remke, H; Preiss, R

doi:10.5414/cpp38209

Cited by 19 publications

(10 citation statements)

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“…Included among these are the use of hammerhead ribozymes against the MDR-1 gene and MDR-1-targeted ASOs (Liu et al, 1996;Dassow et al, 2000;Huesker et al, 2002;Nagata et al, 2002). Hammerhead ribozymes are oligonucleotides that possess enzymatic endoribonucleolytic cleavage activity (Irie et al, 1997).…”

Section: Overcoming Drug Resistance Mediated By Abc Transportersmentioning

confidence: 99%

Strategies for reversing drug resistance

2003

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Section: Overcoming Drug Resistance Mediated By Abc Transportersmentioning

confidence: 99%

Strategies for reversing drug resistance

2003

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“…A recent report also shows that MDR may be due to the modulation of the apoptotic pathway genes [1] . To date, many approaches have been used to overcome MDR, including drugs {cyclosporin A, Ca 2+ channel blocker, arsenic trioxide (As 2 O 3 ) [2,3] }, antisense oligodeoxynucleotide, antisense RNA technology and cytokine therapy [4,5] . There was also a report about the reversal of MDR showing that efficient drug resistance modulators seem to be the most effective MDR reversal agents [6] .…”

Section: Introductionmentioning

confidence: 99%

Effects of Iron Deprivation on Multidrug Resistance of Leukemic K562 Cells

Fang

et al. 2010

Chemotherapy

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Background and Aim: Multidrug resistance (MDR) compromises the efficacy of chemotherapy. Many approaches have been used to reduce MDR; however, the results are poor. It has been reported that iron deprivation downregulates MDR genes. To investigate the relationship of iron with MDR and early growth response gene-1 (EGR1), we investigated the effect of iron deprivation on expression and/or function of multidrug resistance-1 (MDR1), early growth response gene-1 (EGR1), ferritin heavy chain gene (H-Fn) and MDR1-encoded P-glycoprotein (P-gp) in the K562 leukemic cell line. Methods: The cells were stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) and incubated with either FeCl₃ or the iron-chelating drug DFO. The mRNA levels of MDR1, EGR1 and H-Fn were detected by RT-PCR. The protein expression and function of P-gp were measured by immunohistochemical staining and flow cytometry, respectively. Results: DFO significantly reduced the intracellular iron level, and led to ∼70% reduction of MDR1 mRNA, ∼50% of reduction of H-Fn mRNA and ∼30% reduction of P-gp protein in TPA-differentiated K562 cells. The P-gp pump function, measured by daunorubicin exclusion, was also reduced by DFO treatment. Conclusions: These results suggest a close relationship between iron deprivation and reduced MDR1/P-gp expression and function. DFO may be used together with chemotherapeutic drugs to achieve better clinical efficacy.

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“…These authors never observed specific antisense effects with unmodified phosphodiester oligonucleotides. For this reason, and also because to date, very few authors have obtained antisense effects with phosphodiesters (Corrías and Tonini, 1992;Dassow et al, 1998;Efferth and Volm, 1993;Quattrone et al, 1994;Rivoltini et al, 1990) and usually only at very high concentrations or for long treatment periods, we used for a first AMA evaluation the phosphorothioate proposed by Alahari et al (1996). The inhibitory effect of this particular antisense in die presence of Lipofectin has been shown by these authors, and in the present studies, we used Lipofectin under their experimental conditions (cells, concentration, and oligonucleotide), which we assumed to be optimal.…”

Section: Discussionmentioning

confidence: 99%

A Cationic Derivative of Amphotericin B as a Novel Delivery System for Antisense Oligonucleotides

Garcia-Chaumont¹,

Seksek²,

Jollès³

et al. 2000

Antisense and Nucleic Acid Drug Development

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A novel approach based on a plasma membrane permeability-disturbing agent was proposed as an antisense oligonucleotide delivery system. AMA, a derivative of the polyene antibiotic amphotericin B, formed a stable complex when mixed with phosphodiester oligodeoxynucleotides and enhanced the intracellular uptake of a 5' fluoresceinated anti-mdr1 20-mer into NIH-MDR-G185 cells. The nonlabeled phosphorothioate form of the oligodeoxynucleotide, complexed to AMA, inhibited P-glycoprotein expression with better efficiency and less nonspecific effects than when vectorized by Lipofectin. AMA may thus be a good agent for antisense strategy.

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Modulation of multidrug resistance in human leukemia cells with mdr1-targeted antisense oligonucleotides using variable treatment schedules

Cited by 19 publications

References 0 publications

Strategies for reversing drug resistance

Strategies for reversing drug resistance

Effects of Iron Deprivation on Multidrug Resistance of Leukemic K562 Cells

A Cationic Derivative of Amphotericin B as a Novel Delivery System for Antisense Oligonucleotides

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