辐射联合脂质体介导的胞嘧啶脱氨基酶/5-氟胞嘧啶系统体外抑杀人胰腺癌细胞的研究  

Combination therapy of ionizing radiation and lipofectin-mediated cytosine deaminase/5-flurocytosine system for pancreatic cancer cell

作　　者：孙胜 孙诚谊[1] 潘耀振[1] 邓小强[2] 李红伟[2] SUN Sheng;SUN Chengyi;PAN Yaozhen;DENG Xiaoqiang;LI Hongwei(Department of Hepatobiliary Surgery,The First Affiliated Hospital of Guizhou Medical University,Guiyang 550005,P.R.China;Department of Hepatobiliary Surgery,Central Hospital of Luohe City,Luohe,Henan 462000,P.R.China)

机构地区：[1]贵州医科大学第一附属医院肝胆外科,贵阳550005 [2]漯河市中心医院肝胆外科,河南漯河462000

出　　处：《中国普外基础与临床杂志》2020年第9期1078-1083,共6页Chinese Journal of Bases and Clinics In General Surgery

摘　　要：目的探讨辐射联合脂质体介导的胞嘧啶脱氨基酶(CD)/5-氟胞嘧啶(5-FC)系统对胰腺癌的协同治疗作用。方法在脂质体介导下,将CD基因导入人胰腺癌PC3细胞,经G418筛选出稳定表达的克隆。用RT-PCR法鉴定CD基因的整合及表达;MTT法检测给入前药5-FC后细胞的存活率及其旁观者效应;细胞克隆形成实验检测钴-60(60Co)体外照射传代培养后细胞的辐射敏感性。结果CD基因在转染了CD基因细胞中获得了稳定表达;5-FC对转染CD基因细胞具有较强的杀伤及旁观者杀伤效应(P<0.05),联合辐射能进一步增强这一杀伤效应(P<0.05);5-FC处理过的转染了CD基因的PC3细胞对辐射的敏感性明显提高(P<0.05),临床相关剂量(2 Gy)照射时转染CD基因细胞的放射增敏比达到1.5。结论CD/5-FC系统对转染了CD基因的细胞具有明显的辐射增敏效应,联合应用辐射和CD/5-FC系统能显著增强CD/5-FC系统对PC3细胞的杀伤作用。Objective To investigate the synergistic antitumor effects of ionizing radiation and the cytosine deaminase(CD)/5-flurocytosine(5-FC)system therapy in human pancreatic cancer cell.Methods The expression vector containing CD was transfected into the human pancreatic cancer cell line PC3.The clones were picked out after G418 selection.The CD gene integration and expression were confirmed by the RT-PCR.The cytotoxicity to the cells with or without CD and(or)ionizing radiation under the treatment with 5-FC was measured by the MTT assay.The clonogenic assay was used to investigate the radiosensitizing effect of 5-FC on the PC3 cells transfected or untransfected with CD gene.Results The CD gene was stably expressed in the PC3 cells transfected with CD gene.The cytotoxic effect of 5-FC was superior on the PC3 cells transfected than that of untransfected with CD gene(P<0.05)and which were enhanced in combination with the ionizing radiation(P<0.05).The CD/5-FC enhanced the radiosensitivity of PC3 cells transfected with CD gene(P<0.05).The change in the radiosensitivity was quantified by calculating the sensitization enhancement ratio(SER)at the clinically relevant dose of 2 Gy.The SER was 1.5 in the PC3 cells transfected with CD gene by giving ionizing radiation of 2 Gy.Conclusions CD/5-FC system is a potenial radiosensitizer in PC3 cells transfected with CD gene.Ionizing radiation and CD/5-FC system is more effective for killing effect of PC3 cells than ionizing radiation or CD/5-FC system alone.

关 键 词：胰腺肿瘤 辐射 胞嘧啶脱氨基酶 5-氟胞嘧啶 基因治疗 放射增敏 

分 类 号：R735.9[医药卫生—肿瘤]