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

Abstract

Decreased tumour [ 18 F]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 (LD 10 and LD 50 ), 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. 18 FDG 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 LD 50 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.

In vivo imaging of apoptosis

“…75 There is also a report describing a twelve-residue PS-binding peptide discovered by screening a phage library of random peptides. 76 The molecular basis of interaction between the identified peptide, These findings have been confirmed in several studies including: (1) human gastric tumour cells treated with epirubicin, cisplatin and 5-fluorouracil, which were noted that have decreased 18 FDG incorporation and glucose transport, with therapeutic growth inhibition a process that is particularly diminished in cells exhibiting apoptosis; 87 (2) effective anticancer therapy for patients with GIST with the selective tyrosine kinase inhibitor, imatinib mesylate (STI571,Gleevec); 88 and (3) and EGFR kinase inhibition of non-small cell lung cancer with gefitinib. 89 However, because apoptosis must use energy, at least initially, glucose demand may increase temporarily in some clinical situations.…”

Multimodality Molecular Imaging of Apoptosis in Oncology

“…Decreases in FDG uptake have been confirmed in several studies, including a study of human gastric tumor cells treated with epirubicin, cisplatin, and 5-fluorouracil [38]; a study of effective anticancer therapy with the selective tyrosine kinase inhibitor imatinib mesylate (STI571, Gleevec, Novartis) in the care of patients with gastrointestinal stromal tumors [39]; and study of epidermal growth factor receptor kinase inhibition of NSCLC with gefitinib [40]. However, because apoptosis consumes energy, at least initially, glucose demand can increase temporarily in some clinical situations [41].…”

Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer

“…(10) FDG-PET is reportedly also useful for predicting the response to chemotherapy, (11,12) including that of gynecological malignancies. (13)(14)(15) On the cellular level, various chemotherapeutic drugs suppress glucose uptake in cell lines, including ovarian cancer, (16) hematopoietic precursor cells, (17) gastrointestinal stromal tumor (GIST), (18) breast cancer, (19,20) gastric cancer (21) and mesothelioma. (22) Here, we report that glucose uptake decreases over a short period of time after cisplatin treatment in not only ovarian cancer cell lines, but also primary cultured cells derived from patient specimens.…”