含人N-ras反意基因的假型逆转录病毒对裸小鼠体内人肝癌移植瘤生长和N-ras表达的作用

INHIBITION OF HUMAN HEPATOMA GROWTH AND N-ras EXPRESSION IN MICE BY PSEUDOTYPE RETROVIRUS CONTAINING HUMAN N-ras ANTISENSE GENE

含人反意基因的假型逆转录病毒已在许多实验室构建,并用于抑制病毒的或细胞的基因表达。抑制基因活性是一个新的遗传分析方法,其机制是通过一条互补于正常RNA的反意链与有意义链的结合而影响其功能,它的优点是能根据目的基因的转录产物设制有效的反意RNA,研究该基因在细胞中的生物学作用。RNA逆转录病毒因其独特性结构和繁衍形式,已成为理想的基因转移载体。

An amtyphotropic pseudotype retrovirus containing human N-ras antisense gene wasconstructed and packaged with helper cells. It has been proviously demonstrthed thatthe virus did inhibit the growth of human hepatocarcinoma cell line PLC/PRF/5 invitro accompanied with the blockage of P21 expression. Based on these results, this studywas to examine the effect of these viruses on the growth of human hepatoma LTMN4transplanted into nude mice. It was showed that the.retrovirus containing human anti-sense N-ras gene could inhibit the hepatoma in nude mice at a tate of 78%(P<0. 5) ascompared,with saline control. No inhibition was observed in group treated with retrob-virus which contained no N-ras sequenca. These in vivo results lendfurther support thathuma N-ras antisense gene mediated by retrovirus could block the expression of therelevant oncogene and lead to the inhibition of cancer growth.It also provide the basisfor further approaches of gene therapy for human cancer.