Reduction of cisplatin cytotoxicity on human lung cancer cell lines with N-myc amplification by pretreatment with N-myc antisense oligodeoxynucleotides.
Effect of N-myc antisense oligodeoxynucleotide (ODN) on the proliferation of tumor cells and its combined antitumor effect with cisplatin were examined in vitro on human lung cancer cell lines with N-myc amplification. The N-myc oligomer containing the sequence complementary to the ATG initiation codon exhibited a stronger antiproliferative effect on tumor cells than did the oligomer not containing the sequence. A significant difference in the anti-proliferative effect between antisense ODN and sense ODN treatment was observed only on tumor cells with N-myc amplification. Pretreatment with antisense ODN showed a tendency to reduce rather than enhance cisplatin cytotoxicity. Posttreatment with antisense ODN also showed no beneficial effects on cisplatin cytotoxicity. This study suggests that pretreatment with antisense ODN may not be beneficial when combined with chemotherapy.
Mizushima
Y
Y
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Kashii
T
T
Kobayashi
M
M
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002945:Cisplatin / Q000633:toxicity*; D003062:Codon; D004305:Dose-Response Relationship, Drug; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003062:Codon; D016376:Oligonucleotides, Antisense; D002945:Cisplatin; D013936:Thymidine