Metabolic and transcriptional changes in osteosarcoma cells treated with chemotherapeutic drugs.
Two cell lines derived from a lung metastasis of a rat osteosarcoma were treated with cisplatin (CDDP) and two phosphonic acid compounds (AMDP, DADP), AMDP-treated cells showed a decrease in FDG uptake, CDDP and DADP resulted in an increase. A block in G2 or in S and G2 phase was seen after CDDP and AMDP treatment. The changes in the cell cycle fractions were not related to the changes in FDG uptake. Furthermore, the transcription of the glucose transporter and hexokinase genes were elevated in CDDP and decreased in AMDP treated cells. However, the changes in FDG uptake were not fully explained by changes at the transcriptional level. The total uptake of thymidine was elevated although the incorporation of thymidine into DNA decreased. In both cell lines the changes in FDG uptake correlated with the changes in thymidine incorporation into DNA (r = 0.95 and r = 0.83, respectively). Cells with an increased FDG uptake showed a weaker growth inhibition than cells with a decrease in FDG uptake.
Haberkorn
U
U
Department of Oncologic Diagnosis and Therapy, German Cancer Research Center, Heidelberg, Germany.
Oberdorfer
F
F
Klenner
T
T
Strauss
L G
LG
Stöhr
M
M
Wallich
R
R
Altmann
A
A
Kaick
G V
GV
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D009944:Organoplatinum Compounds; D019788:Fluorodeoxyglucose F18; C064516:aminotris(methylenephosphonato)diamminoplatinum (II); C068853:diamminecyclohexanoaminotrismethylenephosphonatoplatinum(II); D003847:Deoxyglucose; D002945:Cisplatin; D013936:Thymidine