摘要
目的：探讨单纯疱疹病毒胸苷激酶（ＨＳＶ－ｔｋ）基因在大肠癌组织细胞中特异地表达，以达到靶向基因治疗的作用。方法：构建以ＣＥＡ基因顺式转录调控序列（ＴＲＳ）驱动ｔｋ 基因的组织特异性重组逆转录病毒载体Ｇ１ＣＥＡｔｋＮａ，然后以重组逆转录病毒上清感染法将重组组织特异性载体及非组织特异性载体分别转导入高分泌ＣＥＡ 的大肠癌ＬｏＶｏ 细胞中，以Ｇ４１８筛选阳性克隆扩增后给予前药更昔洛韦（ＧＣＶ）进行敏感试验。结果：转导组织特异性ｔｋ 基因的ＬｏＶｏ 细胞较转导非组织特异性ｔｋ 基因的ＬｏＶｏ 细胞对ＧＣＶ的敏感性显著增高（Ｐ＜ ０．０１，ｎ＝ ９）。体外实验中还观察到明显的“旁观者效应”。结论：ＣＥＡ ＴＲＳ可调控ＨＳＶ－ｔｋ 基因在ＣＥＡ阳性分泌大肠癌细胞中特异性表达，达到了靶向杀伤肿瘤的目的。
Objective: To study the expression of HSV tk in colorectal carcinoma cell and its role in gene therapy. Methods: The recombinant retroviral vector G1CEAtk1Na was constructed. The retroviral construction and LNtk were produced by CEA highly producing colorectal carcinoma cell line LoVo, and were cultured in G418. The proliferated colonies were treated with GCV. Results: After transfection, LoVo cells transfected by HSV tk gene was more sensitive than their parental cells. Futhermore, the LoVo cells transfected with tissue specific tk gene display a higher anti tumor effect than with non tissue specific tk gene in vitro. Conclusion: CEA TRS can promote the expression of HSK tk in CEA producing colorectal carcinoma cell, thus making it possible for gene therapy.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
1999年第11期869-871,共3页
Academic Journal of Second Military Medical University
基金
国家自然科学基金
关键词
基因肿瘤
HSV-TK基因
自杀基因
colorectal neoplasms
herpes simplex virus thymidine kinase
gene therapy
