Enhanced in vivo tumour response from combination of carboplatin and low-dose c-myc antisense oligonucleotides.
BACKGROUND
Phosphorothioate oligonucleotides ([S]ODNs) contain a modified phosphate backbone. Antisense [S]ODNs targeted to specific oncogenes have been used to varying success in vivo. Carboplatin is a commonly used chemotherapeutic and is associated with chemoresistance in some human tumours. The potential for combined antisense [S]ODNs and carboplatin chemotherapy has only recently been explored in vivo.


METHODS
This study examines the effect of c-myc antisense oligomers delivered in isolation as naked DNA and in combination with carboplatin upon the growth kinetics of an in vivo transplantable adenocarcinoma using rodents.


RESULTS
Tumours treated with a combination of 600 microg of 15-mer c-myc phosphorothioate antisense oligodeoxyribonucleotide and an intravenous administration of carboplatin (3 mg/kg), demonstrated a significant (p<0.05) retardation in tumour growth kinetics relative to a control. Two mismatch antisense controls did not significantly inhibit tumour growth. C-myc protein studies in tumour sections failed to show significant differences in c-myc expression in any of the treated tumours.


CONCLUSIONS
This study demonstrates that carboplatin affects the relative abundance of c-myc and that combination treatment of carboplatin and c-myc phosphorothioate antisense oligonucleotides in vivo results in synergistic tumour retardation.
Walker
T L
TL
School of Biomedical Science, Charles Sturt University, Wagga Wagga, NSW, Australia. towalker@csu.edu
Dass
C R
CR
Burton
M A
MA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D016190:Carboplatin / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D016259:Genes, myc / Q000187:drug effects; D007700:Kinetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000633:toxicity*; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology
D020319:Oligodeoxyribonucleotides, Antisense; D013873:Thionucleotides; D016190:Carboplatin