Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells.

Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. Research Abstract Details 

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Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. Abstract Text:

Fei Shen,Shaoyou Chu,Aimee K Bence,Barbara Bailey,Xinjian Xue,Priscilla A Erickson,Marshall H Montrose,William T Beck,Leonard C Erickson,Fei Shen,Shaoyou Chu,Aimee K Bence,Barbara Bailey,Xinjian Xue,Priscilla A Erickson,Marshall H Montrose,William T Beck,Leonard C Erickson,Fei Shen,Shaoyou Chu,Aimee K Bence,Barbara Bailey,Xinjian Xue,Priscilla A Erickson,Marshall H Montrose,William T Beck,Leonard C Erickson,

P-glycoprotein (Pgp), a membrane transporter encoded by the MDR1 gene in human cells, mediates drug efflux from cells, and it plays a major role in causing multidrug resistance (MDR). Confocal microscopy was used to study in vitro and in vivo drug accumulation, net uptake and efflux, and MDR modulation by P-glycoprotein inhibitors in MDR1-transduced human MDA-MB-435mdr (MDR) cancer cells. The MDR cells were approximately 9-fold more resistant to the anticancer drug doxorubicin than their parental wild-type MDA-MB-435wt (WT) cells. Doxorubicin accumulation in the MDR cells was only 19% of that in the WT cells. The net uptake of doxorubicin in the nuclei of the MDR cells was 2-fold lower than that in the nuclei of the WT cells. Pgp inhibitors verapamil, cyclosporine A, or PSC833 increased doxorubicin accumulation in the MDR cells up to 79%, and it reversed drug resistance in these cells. In living animals, doxorubicin accumulation in MDA-MB-435mdr xenograft tumors was 68% of that in the wild-type tumors. Administration of verapamil, cyclosporine A, or PSC833 before doxorubicin treatment of the animals increased doxorubicin accumulation in the MDR tumors up to 94%. These studies have added direct in vitro and in vivo information on the capacity of the transporter protein Pgp to efflux doxorubicin and on the reversal of MDR by Pgp inhibitors in resistant cancer cells.

Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. Publishing Authors By Initials

F Shen,S Chu,AK Bence,B Bailey,X Xue,PA Erickson,MH Montrose,WT Beck,LC Erickson,F Shen,S Chu,AK Bence,B Bailey,X Xue,PA Erickson,MH Montrose,WT Beck,LC Erickson,F Shen,S Chu,AK Bence,B Bailey,X Xue,PA Erickson,MH Montrose,WT Beck,LC Erickson,

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Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of pharmacology and experimental thera

VOLUME: 324

Page Numbers: 95-102

Journal Abbreviation: J. Pharmacol. Exp. Ther.

ISSN: 1521-0103

DAY: 18

MONTH: 10

YEAR: 2007

Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. Information

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LANGUAGE: eng

NlmUniqueID: 376362

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Grant and Affiliation Information for Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells.

AFFILIATION: Indiana Cancer Center, Cancer Research Institute, R4-Room 168, 1044 West Walnut St., Indianapolis, IN 46202, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA96839-01

ACRONYM: CA

MEDLINETA: J Pharmacol Exp Ther

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