Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro

Smith, Tim A.D.; Sharma, Rituka I.; Wang, Weiguang G.; Welch, Andy E.; Schweiger, Lutz F.; Collie-Duguid, Elaina S.R.

doi:10.1016/j.nucmedbio.2007.07.007

« Previous Next »Nuclear Medicine and Biology
Volume 34, Issue 8 , Pages 955-960, November 2007

Decreased [¹⁸F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro

Tim A.D. Smith
- PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
- Corresponding author. Tel.: +44 01224 553481.
Rituka I. Sharma
- PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
Weiguang G. Wang
- Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
- School of Applied Sciences, University of Wolverhampton, City Campus-South, Wolverhampton WV1 1SB, UK
Andy E. Welch
- PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
Lutz F. Schweiger
- PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
Elaina S.R. Collie-Duguid
- Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK

Received 29 June 2007; received in revised form 10 July 2007; accepted 12 July 2007. published online 20 September 2007.

Abstract

Introduction

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.

Conclusion

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.

Keywords: FDG, MCF7 cells, Glucose transport