Treatment of SW620 cells with Tomudex and oxaliplatin induces changes in 2-deoxy-D-glucose incorporation associated with modifications in glucose transport.
Many studies suggest that changes in the uptake of the glucose analog FDG after therapy, compared with pretreatment uptake, predicts tumor response to therapy. However, clinical interpretation is compromised by a limited understanding of the effect of therapy on FDG and 2-deoxy-D-glucose (DG) uptake at the tumor cell level.


METHODS
Uptake of 2-deoxy-D-[1-(3)H]glucose (3H-DG) by SW620 colonic tumor cells was measured before and 8, 16, 24, and 48 h after treatment with the novel platinum drug oxaliplatin and the novel thymidylate synthase inhibitor Tomudex. Glucose transport was determined by measuring the initial rate of uptake of the nearly nonmetabolized glucose analog 3-O-methyl-D-[1-(3)H]glucose (3H-OMG). The effect of these drugs on cell cycle kinetics was determined using flow cytometry.


RESULTS
Treatment of SW620 cells with oxaliplatin was found to decrease uptake of 3H-DG after up to 24 h, but uptake returned to control levels after longer treatment. The initial decrease in 3H-DG incorporation was associated with a lower rate of glucose transport. Treatment of cells with Tomudex induced an increase in 3H-DG uptake that depended on treatment duration. Both glucose transport and the volume of distribution of 3H-OMG were higher in Tomudex-treated cells than in control cells. Flow cytometry showed that oxaliplatin induced a G2 and M arrest, whereas a buildup of cells in the S phase was associated with Tomudex treatment. Both treatments induced apoptosis in SW620 cells.


CONCLUSIONS
Changes in uptake of DG by SW620 colonic tumor cells responding to therapy is specific to the drug type. Modulation of glucose transport was associated with changes in 3H-DG uptake.
Smith
T A
TA
Department of Nuclear Medicine, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Maisey
N R
NR
Titley
J C
JC
Jackson
L E
LE
Leach
M O
MO
Ronen
S M
SM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D003847:Deoxyglucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011799:Quinazolines / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D013997:Time Factors; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; D014316:Tritium; D003847:Deoxyglucose; D013940:Thymidylate Synthase; C068874:raltitrexed; D005947:Glucose