Limited synergistic effect of antisense oligonucleotides against bcr-abl and transferrin receptor mRNA in leukemic cells in culture.
The synergistic use of antisense oligonucleotides (ASOs) towards the bcr-abl and the transferrin receptor (TfR) mRNA was studied in a chronic myeloid leukemia (CML) cell line, aiming to improve the efficiency of individual ASO treatment. At 20 microM concentration, bcr-abl ASOs reduced cell growth by 40% and was specific for cells that have the translocation: there was a 34% reduction of BCR-ABL protein. The TfR ASO reduced cell growth by 20% and decreased TfR protein by 24%. The ASOs were more potent at reducing cell growth when used in combination (respectively, -20 and -17% than bcr-abl ASO and TfR ASO when used individually at the 10 microM concentration), thus we postulate that there is synergism of action. Cell cycle analysis also revealed that the sub-G1 peak was bigger in the synergistic treatment.
Vasconcelos
M H
MH
Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200, Porto, Portugal.
Beleza
S S
SS
Quirk
C
C
Maia
L F
LF
Sambade
C
C
Guimarães
J E
JE
D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics*; D011990:Receptors, Transferrin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D016044:Fusion Proteins, bcr-abl