摘要
目的:构建含胞嘧啶脱氨酶基因(CD基因)重组腺病毒(AdE1CMVCD),并鉴定;用自杀基因治疗系统(AdE1CMVCD/5-FC)对肺癌进行抑瘤作用的实验研究。方法:体外实验:用不同稀释度的AdE1CMVCD转染人肺癌细胞H460后分别加入不同浓度的5-氟胞嘧啶(5-FC),用MTT法测OD570nm值,按公式计算细胞生长抑制率;体内实验:建立T739鼠肺腺癌荷瘤模型,瘤体内导入AdE1CMVCD,腹腔注射5-FC,观察实验组及各对照组瘤体及生存期差异。结果:该系统转染的人肺癌H460细胞生长抑制率随前药5-FC浓度及感染重组病毒剂量的增加而增加,最大抑制率达61.29%,同时观察到了明显的旁杀伤作用;在体内实验中观察到AdE1CMVCD/5-FC对小鼠肺癌有明显的生长抑制作用,明显延长荷瘤小鼠生存期。结论:本文建立的AdE1CMVCD/5-FC系统体内外对肺癌均有明显的抑制作用,为临床肺癌基因治疗的应用奠定了基础。
Objective:To construct a replication-defective recombinant adenovirus vector containing CMV promoter and CD gene(AdE1CMVCD)and perform AdE1CMVCD/5-FC system study on H460cell growth inhibition experiment in vitro and in vivo.Methods:We infected H460cell with several concentration AdE1CMVCD in vitro,and evaluated the cell growth inhibi-tion rate by MTT method overtime.AdE1CMVCD was directly injected into the established L795tumors-bearing T739mice for observing the diffrence in tumor size and survival days.Re sults:We observed that AdE1CMVCD/5-FC system effectively suppressed the H460cell growth in vitro,and the growth inhibition rate incread in a dose dependence,to the peak of61.29%,and we observed simultaneously the distinct bystander effect.We observed also that there was a signifi-cant difference in tumor size and survival days between the therapeutic group and control group.Conclusion:The established AdE1CMVCD/5-FC system can effectively suppress the pulmonary carcinoma growth in vitro and in vivo.All these observations suggest that the system may have strong potential as a new strategy for suicid gene therapy of pulmonary carcinoma.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2002年第10期739-743,共5页
Chinese Journal of Clinical Oncology
基金
天津市卫生局1999年度科技基金计划项目资助
