[18F]2-Fluoro-2-deoxy-D-glucose incorporation by AGS gastric adenocarcinoma cells in vitro during response to epirubicin, cisplatin and 5-fluorouracil

Stuart Alistair Suttie, K. G. M. Park, T. A. D. Smith

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Decreased tumour [18F]2-fluoro-2-deoxy-D-glucose ((18)FDG) incorporation is related to response however its significance at the cell level in gastro-oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD10 and LD50), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. 18FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V-PE binding ( a measure of apoptosis). Treatment of cells for 48 and 72 h with LD50 doses of cisplatin resulted in reductions in (18)FDG incorporation of 27 and 25% respectively and of 5-fluorouracil reduced (18)FDG incorporation by 34 and 33% respectively: epirubicin treatment reduced incorporation by 30 and 69% respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with (18)FDG incorporation before the recovery period allowed an assessment of the predictive ability of (18)FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in (18)FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between (18)FDG incorporation and cell cycle distribution. Our results show that at the tumour cell level in gastric tumour cells, decreased (18)FDG incorporation and glucose transport, accompanies therapeutic growth inhibition. (18)FDG incorporation is particularly diminished in cells exhibiting apoptosis.

Original languageEnglish
Pages (from-to)902-909
Number of pages8
JournalBritish Journal of Cancer
Volume97
Issue number7
Early online date11 Sep 2007
DOIs
Publication statusPublished - 2 Oct 2007

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Epirubicin
Fluorodeoxyglucose F18
Fluorouracil
Cisplatin
Stomach
Adenocarcinoma
Lethal Dose 50
Pharmaceutical Preparations
Hexokinase
Therapeutics
Esophageal Neoplasms
Apoptosis
Glucose
Cell Cycle
In Vitro Techniques
Activity Cycles
Neoplasms
Annexin A5
Cell Death

Keywords

  • glucose transport
  • hexokinase
  • FDG-PET
  • apoptosis
  • gastric
  • glucose-transporter expression
  • positron-emission-tomography
  • breast-cancer cells
  • tumor-cells
  • FDG uptake
  • preoperative chemotherapy
  • glycolytic metabolism
  • colorimetric assay
  • gene-expression
  • carcinoma cells

Cite this

[18F]2-Fluoro-2-deoxy-D-glucose incorporation by AGS gastric adenocarcinoma cells in vitro during response to epirubicin, cisplatin and 5-fluorouracil. / Suttie, Stuart Alistair; Park, K. G. M.; Smith, T. A. D.

In: British Journal of Cancer, Vol. 97, No. 7, 02.10.2007, p. 902-909.

Research output: Contribution to journalArticle

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abstract = "Decreased tumour [18F]2-fluoro-2-deoxy-D-glucose ((18)FDG) incorporation is related to response however its significance at the cell level in gastro-oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD10 and LD50), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. 18FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V-PE binding ( a measure of apoptosis). Treatment of cells for 48 and 72 h with LD50 doses of cisplatin resulted in reductions in (18)FDG incorporation of 27 and 25{\%} respectively and of 5-fluorouracil reduced (18)FDG incorporation by 34 and 33{\%} respectively: epirubicin treatment reduced incorporation by 30 and 69{\%} respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with (18)FDG incorporation before the recovery period allowed an assessment of the predictive ability of (18)FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in (18)FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between (18)FDG incorporation and cell cycle distribution. Our results show that at the tumour cell level in gastric tumour cells, decreased (18)FDG incorporation and glucose transport, accompanies therapeutic growth inhibition. (18)FDG incorporation is particularly diminished in cells exhibiting apoptosis.",
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N2 - Decreased tumour [18F]2-fluoro-2-deoxy-D-glucose ((18)FDG) incorporation is related to response however its significance at the cell level in gastro-oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD10 and LD50), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. 18FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V-PE binding ( a measure of apoptosis). Treatment of cells for 48 and 72 h with LD50 doses of cisplatin resulted in reductions in (18)FDG incorporation of 27 and 25% respectively and of 5-fluorouracil reduced (18)FDG incorporation by 34 and 33% respectively: epirubicin treatment reduced incorporation by 30 and 69% respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with (18)FDG incorporation before the recovery period allowed an assessment of the predictive ability of (18)FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in (18)FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between (18)FDG incorporation and cell cycle distribution. Our results show that at the tumour cell level in gastric tumour cells, decreased (18)FDG incorporation and glucose transport, accompanies therapeutic growth inhibition. (18)FDG incorporation is particularly diminished in cells exhibiting apoptosis.

AB - Decreased tumour [18F]2-fluoro-2-deoxy-D-glucose ((18)FDG) incorporation is related to response however its significance at the cell level in gastro-oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD10 and LD50), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. 18FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V-PE binding ( a measure of apoptosis). Treatment of cells for 48 and 72 h with LD50 doses of cisplatin resulted in reductions in (18)FDG incorporation of 27 and 25% respectively and of 5-fluorouracil reduced (18)FDG incorporation by 34 and 33% respectively: epirubicin treatment reduced incorporation by 30 and 69% respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with (18)FDG incorporation before the recovery period allowed an assessment of the predictive ability of (18)FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in (18)FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between (18)FDG incorporation and cell cycle distribution. Our results show that at the tumour cell level in gastric tumour cells, decreased (18)FDG incorporation and glucose transport, accompanies therapeutic growth inhibition. (18)FDG incorporation is particularly diminished in cells exhibiting apoptosis.

KW - glucose transport

KW - hexokinase

KW - FDG-PET

KW - apoptosis

KW - gastric

KW - glucose-transporter expression

KW - positron-emission-tomography

KW - breast-cancer cells

KW - tumor-cells

KW - FDG uptake

KW - preoperative chemotherapy

KW - glycolytic metabolism

KW - colorimetric assay

KW - gene-expression

KW - carcinoma cells

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DO - 10.1038/sj.bjc.6603971

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JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

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