Inhibitory effects of antisense oligodeoxynucleotides targeting c-myc mRNA on smooth muscle cell proliferation and migration.

摘要: Abstract Smooth muscle cell (SMC) proliferation and migration play pivotal roles in restenosis following angioplasty. c-myc is an immediate early response gene induced by various mitogens, several lines of evidence derived from experiments using transformed or hematopoietic lines, transgenic mice, suggest its protein product plays a role numerous signaling transduction pathways, including those modulating division. We therefore reasoned that strategy employing oligodeoxynucleotides (ODNs) complementary to mRNA (antisense ODNs) might be potent inhibitors SMC and, perhaps, migration. To evaluate this concept, we tested antisense ODNs targeted (15- 18-mer different sequences) introducing them individually into the medium cultured rat aortic SMCs. Phosphoroamidate-modified were employed retard degradation. Antisense inhibited, concentration-dependent manner, Maximal inhibitory effect was 50% for > 90% These effects associated with decreased expression c-myc-encoded Western immunoblotting immunocytochemical staining. same nucleotides but scrambled sequence caused no effect. results indicate involved signal pathways mediating vitro model employed. The also potential strategies designed inhibit prevention coronary restenosis.