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 proliferat ion of tumor cells and its combined antitumor effect with cisplatin we t examined in vitro on human lung cancer cell lines with N-myc amplifi cation. The N-myc oligomer containing the sequence complementary to th e ATG initiation codon exhibited a stronger antiproliferative effect o n tumor cells than did the oligomer not containing the sequence. A sig nificant difference in the anti-proliferative effect between antisense ODN and sense ODN treatment was observed only on tumor cells with N-m yc 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 cytotoxi city. This study suggests that pretreatment with antisense ODN may not be beneficial when combined with chemotherapy.