Modification of the sensitivity to cisplatin with c-myc over-expression or down-regulation in colon cancer cells.

Human colon cancer SW480 cells express the c-myc gene. On the other hand, SW480DDP cell lines resistant to cisplatin exhibited decreased c-myc gene expression, but their cell growth rates remained similar to those of their parental cells. Antisense oligonucleotides to c-myc inhibited c-myc expression and induced increased resistance to cisplatin in SW480 cells. In contrast, SW480DDP cells showed increased c-myc expression and reversed sensitivity to cisplatin when these cells were transfected with c-myc cDNA from the pLNCX plasmid. Moreover, SW480DDP cells transfected with c-myc cDNA induced apoptosis when exposed to cisplatin, but not SW480 cells transfected with an antisense sequence for c-myc. Transfection either with a c-myc antisense sequence or c-myc cDNA to these cells did not change their growth rates. Thus enforced expression of c-myc in SW480 and SW620 lines sensitizes cells to cisplatin-induced apoptosis, whereas the down-regulation of c-myc in SW480DDP and SW620DDP increases cisplatin resistance when using antisense strategy.