阳离子脂质体介导pE-CEA-cd-tk对CEA阳性肺癌的杀伤作用  

The killing effects of pE-CEA-cd-tk/5-FC+GCV system mediated by cationic liposome targeted to CEA positive lung cancer cells

作　　者：李芳[1] 伍新尧[2] 罗超权[1] 

机构地区：[1]中山医科大学生物化学教研室,510089 [2]中山医科大学法医学教研室,510089

出　　处：《肿瘤》2002年第1期35-38,共4页Tumor

摘　　要：目的　增强E .colicd/HSV 1tk自杀基因的细胞毒性 ,实现阳离子脂质体介导pE CEA cd tk/5 FC +GCV体系靶向杀伤CEA阳性肺癌。方法　PCR法分别扩增出CMV增强子 ,CEA启动子 ,cd tk ,构建真核表达载体 pE CEA cd tk ;MTT法检测pE CEA cd tk/5 FC +GCV体系的体外细胞毒性。体内实验采用肺腺癌细胞SPC A 1裸鼠皮下移植瘤模型。通过肿瘤局部或鼠尾静脉注射脂质体 /pE CEA cd tk复合物 ,腹腔注射GCV +5 FC前体药物进行治疗。结果　阳离子脂质体介导pE CEA cd tk/5 FC +GCV体系体外可靶向杀伤CEA阳性肺癌细胞 ,这种杀伤作用存在显著的细胞差异 ;体内可抑制小鼠皮下肺肿瘤结节的生长 ,荷瘤鼠存活期延长。结论　阳离子脂质体介导 pE CEA cd tk/5 FC +GCV体系体内外对CEA阳性肺癌均具有较强的杀伤作用。Objective To enhance the cytotoxic effects of E.coli cd/HSV 1tk suicide genes, and targeted therapy of CEA positive lung cancer by pE CEA cd tk/5 FC+GCV system mediated by cationic liposome. Methods CMV enhancer,CEA promotor and cd tk fusion gene were obtained by PCR. Based on pcDNA3,eukaryotic expression vector pE CEA cd tk was constracted. The in vitro cytotoxic effects of pE CEA cd tk/5 FC+GCV system were measured by MTT assay. In vivo experiments, nude mice were inoculated subcutaneously with SPC A 1 pulmonary adenocarcinoma cells and received cationic liposome/pE CEA cd tk complexes by intratumoral injection or tail vein injection followed by continuous intraperitoneal (i.p.) injection with 5 FC and GCV prodrugs. Results The pE CEA cd tk/5 FC+GCV system mediated by cationic liposome had strong killing effect on CEA positive lung cancer cells in vitro, and this effect was significantly different in various types of cells. A significant reduction in tumor size and prolongation of survival period were observed in the tumor bearing nude mice received treatment. Conclusion THe pE CEA cd tk/5 FC+GCV system mediated by cationic liposome has strong killing effect on CEA positive lung cancer in vitro and in vivo. It may be applicable on clinical therapy study.

关 键 词：阳性肺肿瘤 自杀基因 阳离子脂质体 CEA启动子 CMV增强子 

分 类 号：R734.2[医药卫生—肿瘤]