Research Article
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Published Online: 22 August 2005

MRP-1 Protein Expression and Glutathione Content of In Vitro Tumor Cell Lines Derived from Human Glioma Carcinoma U-87-MG Do Not Interact with 99mTc-Glucarate Uptake

Publication: Cancer Biotherapy & Radiopharmaceuticals
Volume 20, Issue Number 4

Abstract

The main cause of the multidrug resistance (MDR) of glioma cells is the overexpression of MRP-1, often associated with high levels of glutathione (GSH). We investigated whether MRP-1-related GSH content can influence 99mTc-glucarate entry by comparing its uptake with that of 99mTc-sestamibi (MIBI), an MRP- 1 probe, in an in vitro model of a sensitive cell line (U-87-MG) and a resistant derived cell line expressing MRP-1 (U-87-MG-R). Drug resistance was assessed by immunoblotting, GSH measurement, and Alamar Blue™ assay. To correlate MDR phenotype with tracer accumulation, uptakes were performed with and without modulators and after GSH depletion. Similar accumulation of 99mTc-glucarate was observed in the two cell lines, and the use of MDR reversals did not enhance its uptake. Our results clearly demonstrate that 99mTc-glucarate uptake is not related to MRP-1 expression or GSH levels. In contrast, 99mTc- MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of 99mTc-glucarate and 99mTc-MIBI may be a useful tool for the noninvasive detection of malignant sites and their chemoresistance status.

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Published In

cover image Cancer Biotherapy and Radiopharmaceuticals
Cancer Biotherapy & Radiopharmaceuticals
Volume 20Issue Number 4August 2005
Pages: 391 - 400
PubMed: 16114987

History

Published online: 22 August 2005
Published in print: August 2005

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Nathalie Perek
Laboratory of Biophysics, Research Group EA 3063 "Cellular Survival and Adhesion in Tumors and Grafts"—Faculty of Medicine, Saint-Etienne, France.
Nathalie Le Jeune
Laboratory of Biophysics, Research Group EA 3063 "Cellular Survival and Adhesion in Tumors and Grafts"—Faculty of Medicine, Saint-Etienne, France.
Delphine Denoyer
Laboratory of Biophysics, Research Group EA 3063 "Cellular Survival and Adhesion in Tumors and Grafts"—Faculty of Medicine, Saint-Etienne, France.
Francis Dubois
Laboratory of Biophysics, Research Group EA 3063 "Cellular Survival and Adhesion in Tumors and Grafts"—Faculty of Medicine, Saint-Etienne, France.

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