反义c－Ha－rasDNA对人胃癌转化细胞致癌性的抑制  

Inhibition of antisense DNA and its derivative on gas- tric transforlned cell carcinogenicity

作　　者：杨定成[1] 李通[1] 徐文怀[1] 

机构地区：[1]北京医科大学第一临床学院外科

出　　处：《中华外科杂志》1995年第1期26-28,共3页Chinese Journal of Surgery

基　　金：国家自然科学基金;天然和仿生药物国家重点实验室资助课题

摘　　要：作者人工合成了一条１５聚反义ｃ－Ｈａ－ｒａｓＤＮＡ，此反义ＤＮＡ与ｃ－Ｈａ－ｒａｓ基因转录起始区域的序列互补。其可以在转录和翻译水平上阻断ｃ－Ｈａ－ｒａｓ基因表达，使胃癌转化细胞的一些恶性表型（包括生长速度、软琼脂中集落形成，裸鼠致瘤性和分化程度）发生逆转。在反义ＤＮＡ的５’－端共价连接一个补骨脂素基团后，其生物学活性显著增强，和靶基因序列不完全配对的对照寡聚核苷酸链不具有上述肿瘤抑制效应。结果提示：反义ＤＮＡ及其衍生物是进行肿瘤基因治疗有效工具之一。AbstractIn this study,an antisense c-Ha-ras DNA was synthesized.It was a complementary oligonucleotide chain to the seouence of initiation position of c-Ha-ras gene transcription. We found that the antisense DNA blocked the gene expression at the level of transcrip- tion and translation and partially reverted the malig- nant phenotypeed of gastric transformed cells,in- cluding their growth rate,colonies formation in soft agar,tumorigenicity in nude mice and different grade. when the 5-end of the antisense DNA was covalentlyIinked with psoralen group,its biological effects weresignificantly enhanced. No effect of tumor inhibitionwas found in control oligonucleotide chains not com-plete complementary to the sequence of target gene.These results indicate that antisense DNA and itsderivative are effective in tumor gene therapy.

关 键 词：基因 表达调节 遗传转录 胃肿瘤 DNA C-H-ras 

分 类 号：R735.203[医药卫生—肿瘤]