Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro.
BACKGROUND
Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18F]fluoro-2-deoxy-d-glucose (FDG) incorporation, as compared with sensitive cells.


METHODS
FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells.


RESULTS
FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration.


CONCLUSIONS
FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.
Smith
Tim A D
TA
PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. t.smith@biomed.abdn.ac.uk
Sharma
Rituka I
RI
Wang
Weiguang G
WG
Welch
Andy E
AE
Schweiger
Lutz F
LF
Collie-Duguid
Elaina S R
ES
D001693:Biological Transport, Active / Q000187:drug effects; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D005472:Fluorouracil