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Study on the mechanism of multi-drug resistance reversed by quercetin in leukemic K562 adriamycin resistant cell lines

Ouyang Ren-ron

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Abstract

Objective To investigate the mechanism of multi-drug resistance(Mdr) reversed by Quercetin mainly in respect of membrane transporters. Methods MTT cell viability assay was adapted for verifying the chemo-sensitization of Quercetin to Daunorubicin(DNR), and the reverse concentration was determined. The expression of Mdr1 gene and its protein product P-glycoprotein(P-gp) were analysed by RT-PCR and flow cytometry with monoclonal antibody. By confocal laser scanning microscopy,the subcellular distribution of DNR in K562/S and K562/ADM cell lines was observed before and after exposing to Quercetin. Results Comparing with K562/S,20~40μmol/L Quercetin in vitro can remarkably increase the sensitivity of K562/ADM to DNR,down-regulate the expression of Mdr1 gene and its protein product P-gp,restore the abnormal subcellular distribution of DNR,so as to reverse multidrug resistance. Conclusion Quercetin may become a candidate of effective multi-drug resistance-reversing agent with low toxicity in leukemia chemotherapy.

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Objective To investigate the mechanism of multi-drug resistance(Mdr) reversed by Quercetin mainly in respect of membrane transporters. Methods MTT cell viability assay was adapted for verifying the chemo-sensitization of Quercetin to Daunorubicin(DNR), and the reverse concentration was determined. The expression of Mdr1 gene and its protein product P-glycoprotein(P-gp) were analysed by RT-PCR and flow cytometry with monoclonal antibody. By confocal laser scanning microscopy,the subcellular distribution of DNR in K562/S and K562/ADM cell lines was observed before and after exposing to Quercetin. Results Comparing with K562/S,20~40μmol/L Quercetin in vitro can remarkably increase the sensitivity of K562/ADM to DNR,down-regulate the expression of Mdr1 gene and its protein product P-gp,restore the abnormal subcellular distribution of DNR,so as to reverse multidrug resistance. Conclusion Quercetin may become a candidate of effective multi-drug resistance-reversing agent with low toxicity in leukemia chemotherapy.

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Available abstract

Objective To investigate the mechanism of multi-drug resistance(Mdr) reversed by Quercetin mainly in respect of membrane transporters. Methods MTT cell viability assay was adapted for verifying the chemo-sensitization of Quercetin to Daunorubicin(DNR), and the reverse concentration was determined. The expression of Mdr1 gene and its protein product P-glycoprotein(P-gp) were analysed by RT-PCR and flow cytometry with monoclonal antibody. By confocal laser scanning microscopy,the subcellular distribution of DNR in K562/S and K562/ADM cell lines was observed before and after exposing to Quercetin. Results Comparing with K562/S,20~40μmol/L Quercetin in vitro can remarkably increase the sensitivity of K562/ADM to DNR,down-regulate the expression of Mdr1 gene and its protein product P-gp,restore the abnormal subcellular distribution of DNR,so as to reverse multidrug resistance. Conclusion Quercetin may become a candidate of effective multi-drug resistance-reversing agent with low toxicity in leukemia chemotherapy.

Key concepts: Daunorubicin, K562 cells, Flow cytometry, P-glycoprotein, Multiple drug resistance, Pharmacology, MTT assay, Cytotoxicity

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