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.
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 (99m)Tc-glucarate entry by comparing its uptake with that of (99m)Tc-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 (99m)Tc-glucarate was observed in the two cell lines, and the use of MDR reversals did not enhance its uptake. Our results clearly demonstrate that (99m)Tc-glucarate uptake is not related to MRP-1 expression or GSH levels. In contrast, (99m)Tc- MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of (99m)Tc-glucarate and (99m)Tc-MIBI may be a useful tool for the noninvasive detection of malignant sites and their chemoresistance status.
Perek
Nathalie
N
Laboratory of Biophysics, Research Group EA 3063 Cellular Survival and Adhesion in Tumors and Grafts-Faculty of Medicine, Saint-Etienne, France. nathalie.perek@univ-st-etienne.fr
Le Jeune
Nathalie
N
Denoyer
Delphine
D
Dubois
Francis
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D015153:Blotting, Western; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000473:pathology*; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009362:Neoplasm Metastasis; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010641:Phenotype; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C067171:technetium Tc 99m glucarate; D005978:Glutathione; D005937:Glucaric Acid