反义核酸药物与抗肿瘤研究

现在各国正在利用反义技术发展一类由核酸组成的新型药物,即反义核酸药物。我们合成了5种血管内皮生长因子(VEGF)的反义寡聚脱氧核苷酸(ODN_S)。测定了它们在S180肿瘤细胞中对VEGF表达的抑制作用,还测定了它们在鼠角膜肿瘤模型上抑制由肿瘤引起的新生血管形成和肿瘤的生长。结果表明,部分硫代的或发夹结构修饰的ODNs均可有效抑制VEGF的表达、肿瘤的生长和新生血管的形成。线性的ODN效果不好。两种作用于不同位点的ODN联合使用可得到最好的效果。因此反义VEGF寡聚脱氧核苷酸有望成为抗肿瘤和抗新生血管形成的新型药物。

Antisense Nucleic Acid Drug and Antitumor Research

Nowadays a new kind of drugs made of nucleic acid is being developed by antisense technology.Five kinds of antisense oligodeoxynucleotides(ODNs) of vascular endothelial growth factors(VEGF) were synthesized.The inhibition of the VEGF modifications and sequences was determined. Their inhibition of angiogenesis and tumor growth was also determined. Results showed that ODNs with partial phosphorothiate modification, or with hairpin structure could effectively inhibit the VEGF expres-sion , tumor - induced angiogenesis and tumor growth with a tumor model on the cornea of rat, but the linear ODN could not. The use of 2 ODNs at different sites gave the best results, so antisense VEGF ODNs can hopefully become new drug with antitumor and anitangiogenesis activity.