Inhibition of rat aortic smooth muscle cell proliferation by chimeric phosphorothioate antisense c- myc oligodeoxynucleotide

AIM:Investigate the role of c- myc gene expression in the signal transduction pathways mediating smooth muscle cell (SMC) proliferation and the effect of chimeric phosphorothioate antisense c- myc oligodeoxynucleotide (AS-ODN) on rat aortic SMC proliferation.METHODS:Chimeric phosphorothioate c- myc AS-ODN targeting the 1st 5 codons of translation initiation region of c- myc mRNA was introduced by lipofectin and its inhibitory effect on SMC proliferation was observed by cell count and -TdR incorporation. RESULTS:c- myc AS-ODN markedly suppressed proliferation of not only SMC stimulating from quiescent state but also exponential SMC. The inhibitory effect of c- myc AS-ODN on SMC proliferation was decreased and even abrogated by adding sense c- myc ODN. The larger dose there was, the greater inhibitory effect of c- myc AS-ODN on SMC proliferation there was. A single administration of c- myc AS-ODN had lasting action.Sense c- myc ODN and mismatch c- myc ODN had no significant effect on SMC proliferation compared with control. CONCLUSIONS:c- myc AS-ODN inhibited SMC proliferation in a dose-dependent and sequence-specific manner. This investigation indicates that c- myc gene product is involved in the signal transduction pathways mediating SMC proliferation and provides a basis for future study of the potential role of antisenese strategy using c- myc AS-ODN designed to inhibit SMC proliferation for the prevention of coronary restenosis