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Non-radioactive 2-deoxy-2-fluoro-D-glucose inhibits glucose uptake in xenograft tumours and sensitizes HeLa cells to doxorubicin in vitro.

ABSTRACT: A glucose analog called 2-deoxy-D-glucose (2DG) has been successfully used to sensitize cancer cells to ROS-inducing cancer treatments such as ionizing radiation, through the inhibition of glycolysis. However, the use of 2DG can be limited by several factors such as availability, non-specific cytotoxicity, and chemoresistance under hypoxic conditions. The purpose of this study was to investigate the use of non-radioactive 2-deoxy-2-fluoro-D-glucose (19FDG), a drug that potentially addresses current limitations of 2DG. The effectiveness of using either 2DG or 19FDG in combination with doxorubicin (Dox) in HeLa cells was determined in both normoxia and hypoxia. We have also shown that under both oxygen conditions, 19FDG-treated cells produce less lactate than 2DG-treated cells, an important finding that suggests improved inhibition of glycolysis, the preferential pathway for cancerous cells. When used in combination with Dox, we have demonstrated a significant decrease in the number of viable cells, with the effect of 19FDG remaining stable across both normoxic and hypoxic conditions. Moreover, the assessment of apoptosis and necrosis revealed that 19FDG maintained its ability to sensitize HeLa cells to Dox in hypoxia, but 2DG was only effective under normoxic conditions. The retained effectiveness of 19FDG in combination with Dox under hypoxic conditions, suggests that 19FDG may be efficacious for sensitizing hypoxic regions of solid tumour masses. Importantly, the ability of 19FDG to inhibit glucose uptake in vivo was also confirmed using positron emission tomography (PET) of xenograft tumours. The results displayed here suggest 19FDG is a promising combination therapy, which may lead to decreased ROS scavenging via glycolysis, and enhanced treatment success.

SUBMITTER: Niccoli S

PROVIDER: S-EPMC5667878 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Non-radioactive 2-deoxy-2-fluoro-D-glucose inhibits glucose uptake in xenograft tumours and sensitizes HeLa cells to doxorubicin in vitro.

Niccoli Sarah S Boreham Douglas R DR Phenix Christopher P CP Lees Simon J SJ

PloS one 20171102 11

A glucose analog called 2-deoxy-D-glucose (2DG) has been successfully used to sensitize cancer cells to ROS-inducing cancer treatments such as ionizing radiation, through the inhibition of glycolysis. However, the use of 2DG can be limited by several factors such as availability, non-specific cytotoxicity, and chemoresistance under hypoxic conditions. The purpose of this study was to investigate the use of non-radioactive 2-deoxy-2-fluoro-D-glucose (19FDG), a drug that potentially addresses curr ...[more]

PMID: 29095925

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Project description:BackgroundSkeletal muscle glucose utilization is an important component of whole-body glucose consumption in normal humans. Fluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) is a non-invasive molecular imaging probe for evaluating tissue glucose utilization. It remains unclear whether or not 18 F-FDG uptake by skeletal muscle has utility as a biomarker for metabolic derangement. We investigated the utility of measurement of muscle 18 F-FDG positron emission tomography/computed tomography uptake as a surrogate marker for existing and incipient metabolic abnormalities.MethodsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptakes of insulin-sensitive organs (liver, pancreas, mesenteric visceral fat, psoas muscle, and abdominal subcutaneous fat) and their association with metabolic abnormalities were evaluated in an experimental group comprising 91 men and 66 women (mean age 49.9 ± 11.1 years). In this cross-sectional cohort, we assessed the predictive power of the optimal cut-off 18 F-FDG uptake [maximum standardized uptake value (SUVmax )]. We confirmed its feasibility and reliability for diagnosis of existing and incipient metabolic derangement in the validation group (longitudinal cohort comprising 91 men and 67 women; mean age 52.6 ± 7.9 years).ResultsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptake (SUVmax ) of psoas muscle was strongly correlated with clinical metabolic parameters in the experimental group. It was positively correlated with waist circumference, body mass index, fasting glucose, triglyceride, systolic and diastolic pressure, and negatively correlated with high-density lipoprotein cholesterol levels (for all, P < 0.05). SUVmax of the psoas muscle also showed the best area under the curve value (0.779) as a predictor of metabolic syndrome (MetS) in the experimental group. Using the optimal cut-off SUVmax of 1.34, the sensitivity, specificity, accuracy, positive, and negative predictive value for predicting existing MetS in the experimental group were 70.0%, 84.6%, 80.9%, 60.9%, and 89.2%, respectively. In the validation group, corresponding values were 47.6%, 92.3%, 86.1%, 50.0%, and 91.6%, respectively. Existing and incipient MetS were significantly higher in subjects with high 18 F-FDG uptake by the psoas muscle (SUVmax > 1.34). Subjects with higher psoas muscle SUVmax had a 3.3-fold increased risk of developing MetS (P = 0.017).ConclusionsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptake of psoas muscle is a promising surrogate marker for existing and incipient metabolic derangement.

Dataset Information

Non-radioactive 2-deoxy-2-fluoro-D-glucose inhibits glucose uptake in xenograft tumours and sensitizes HeLa cells to doxorubicin in vitro.

Publications

Non-radioactive 2-deoxy-2-fluoro-D-glucose inhibits glucose uptake in xenograft tumours and sensitizes HeLa cells to doxorubicin in vitro.

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