RNAi depletion of deoxycytidine and deoxyguanosine kinase in human leukemic CEM cells.
Resistance toward nucleoside analogues is often due to decreased activities of the activating enzymes deoxycytidine kinase (dCK) and/or deoxyguanosine kinase (dGK). With small interfering RNA (siRNA), dCK and dGK were downregulated by approximately 70% in CEM cells and tested against six nucleoside analogues using the methyl thiazol tetrazolium assay. SiRNA-transfected cells reduced in dCK activity were 3- to 6-fold less sensitive to CdA, AraC, and CAFdA. The sensitivity to AraG and FaraA was unchanged, while the sensitivity toward gemcitabine was significantly increased. dGK depletion in cells resulted in lower sensitivity to FaraA, dFdC, CAFdA, and AraG, but slightly higher sensitivity to CdA and AraC.
Fyrberg
Anna
A
Division of Clinical Pharmacology, Department of Medicine and Health, Linköping University, Linköping, Sweden. anfyr@imv.liu.se
Albertioni
Freidoun
F
Lotfi
Kourosh
K
D045744:Cell Line, Tumor; D003842:Deoxycytidine Kinase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009705:Nucleosides / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
D009705:Nucleosides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D003842:Deoxycytidine Kinase