Measurement of FDG uptake documents that a direct effect on cell metabolism is a prerequisite of anticancer action of metformin in lung and breast cancer (Abstract in rivista)

Type
Label
  • Measurement of FDG uptake documents that a direct effect on cell metabolism is a prerequisite of anticancer action of metformin in lung and breast cancer (Abstract in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Alternative label
  • Cecilia Marini; M. Massollo; B. Salani; A. Amaro; D. Maggi; S. Capitanio; S. Maffioli; S. Morbelli; M. Riondato; C. Massara; A. Esposito; R. Cordera; U. Pfeffer; Gianmario Sambuceti. (2012)
    Measurement of FDG uptake documents that a direct effect on cell metabolism is a prerequisite of anticancer action of metformin in lung and breast cancer
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cecilia Marini; M. Massollo; B. Salani; A. Amaro; D. Maggi; S. Capitanio; S. Maffioli; S. Morbelli; M. Riondato; C. Massara; A. Esposito; R. Cordera; U. Pfeffer; Gianmario Sambuceti. (literal)
Pagina inizio
  • S243 (literal)
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  • 39 (literal)
Rivista
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  • Suppl-2 (literal)
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  • CNR Institute of Bioimages and Molecular Physiology, Milan, Section of Genoa, Italy, Genova, Italy. Nuclear Medicine, Dept. of Internal Medicine, University of Genoa and IRCCS AOU San Martino - IST, Genova, Italy. Endocrinology and Medicine, University of Genova, Genova, Italy, Genova, Italy. Integrated Molecular Pathology Unit, IRCCS AOU San Martino - IST, Genova, Italy, Genova, Italy. (literal)
Titolo
  • Measurement of FDG uptake documents that a direct effect on cell metabolism is a prerequisite of anticancer action of metformin in lung and breast cancer (literal)
Abstract
  • Aim. High concentrations of metformin have been reported to reduce growth rate of cell lines derived from different types of human cancer. This study aims to verify whether this effect is mediated by a reduction in glucose consumption in cells derived from Calu-1 line as a model of human non-small-cell lung cancer (NSCLC) and from MDA-MB-231 line as a model of breast cancer. Materials and Methods. Glucose consumption was evaluated by incubating 1.5 x 106 cells with 1 ml of saline containing 148 KBq of 18F-fluorodeoxyglucose (FDG). Tracer exposure was maintained for one hour at 37° C before measurement of labeling yield with a gamma-counter. Evaluations were performed under control conditions and after 24 hours exposure to different concentrations of metformin (1, 5 and 10 mM) with or without type 1 insulin-like growth factor (IGF1) at the concentration of 1.7 microM to verify the role of glucose transporters. The activated, phosphorylated forms of AMPK (p-AMPK) and IGF1 receptors (p-IGF-1R) were also measured under all conditions. Results. In both cell populations, 1mM metformin concentration slightly (but not significantly) increased FDG uptake, independently from the presence of IGF1. At the concentration of 5 mM, the drug decreased FDG uptake in Calu-1 (from 31±8% to 16±1%, p<0.05) but not in MDA-MB-231 (from 50±7% to 46±17%, p=ns). On the contrary, the highest metformin concentration decreased FDG uptake both in Calu-1 cells (to 3.3±0.4%, p<0.01 vs control) and in MDA-MB-231 (to 16±3%, p<0.01 vs control). This metabolic effect of metformin was not modified by the presence of IGF1 in any case. Interestingly, high (5 and 10 mM) metformin concentrations induced a significant increase in p-AMPK and a significant reduction in the p-IGF-1R. Conclusion. High concentrations of metformin decrease glucose consumption both in Calu-1 and in MDA-MB-231 cells. This drug effect on metabolism of lung and breast cancer is independent from the effect of IGF-1R and may open new strategies for metformin use in cancer prevention or treatment. On the diagnostic field, this metabolic effect might reduce the sensitivity of PET-CT imaging in cancer patients with diabetes treated with this drug. (literal)
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