反义c-myc寡脱氧核苷酸对血管平滑肌细胞增殖、迁移和凋亡的影响

为研究硫代磷酸修饰的反义c-myc寡脱氧核苷酸(ODN)对血管平滑肌细胞(SMC)的增殖、迁移及凋亡的影响。应用脂质体分别介导硫代磷酸修饰的反义c-mycODN、正义c-mycODN和错配c-mycODN进入体外培养的大鼠主动脉SMC内,观察其对SMC细胞c-myc表达、增殖、迁移和凋亡的影响。结果:①反义ODN降低c-myc蛋白的表达。②反义c-mycODN抑制SMC增殖、迁移,并诱导SMC凋亡。而正义ODN及错配ODN则无上述作用。结果提示:应用反义技术抑制c-myc表达在防治经皮腔内冠状动脉成形术(PTCA)术后再狭窄中具有潜在作用。

Antisense c-myc Oligodeoxynucleotides Inhibited Proliferation, Migration of Vascular Smooth Muscle Cells and Induced Apoptosis by Downregulation of c-myc Expression

To investigate the effects of synthetic phosphorothioate-modified antisense oligodeoxynucleotides(ODN), which is complementary to the first five codens of c-myc mRNA(AS ODN), on proliferation, migration and apoptosis of vascular smooth muscle cells(SMC), AS ODN were introduced into cultured rat arotic SMCs by lipofectin, observed that antisense ODN inhibited SMC proliferation and migration, and induced SMC apoptosis. These effects were associated with decreased expression of c-myc encoded protein which was shown by western blot. ODN with the same nucleotides but a sense sequence or a mismatched sequence did not show same effects as AS ODN did. The results suggested a potential role of antisense strategies designed to inhibit c-myc expression for prevention of restenosis following angioplasty.