论文部分内容阅读
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。有望用于CEA阳性肺癌的治疗
Objective To enhance the cytotoxicity of 1tk suicide gene of E.colicd / HSV and to achieve cationic liposome-mediated targeting of CEA-positive lung cancer by pE CEA cd tk / 5 FC + GCV system. Methods CMV enhancer, CEA promoter and cd tk were amplified by PCR. The eukaryotic expression vector pE CEA cd tk was constructed. The cytotoxicity of pE CEA cd tk / 5 FC + GCV system was detected by MTT assay. In vivo experiments, lung adenocarcinoma cell line SPC A 1 xenografts model was established. The liposome / pE CEA cd tk complex was injected either locally into the tumor or into the tail vein of the rat and intraperitoneally injected with the GCV + 5 FC prodrug. Results The cationic liposome-mediated pE CEA cd tk / 5 FC + GCV system could target and kill CEA positive lung cancer cells in vitro. There were significant cell differences in this killing effect. In vivo, it could inhibit the growth of subcutaneous lung tumor nodules, Tumor bearing mice prolonged survival. Conclusion The cationic liposome-mediated pE CEA cd tk / 5 FC + GCV system has a strong killing effect on CEA positive lung cancer both in vitro and in vivo. It is expected to be used in the treatment of CEA-positive lung cancer