吉西他滨联合溶瘤型腺病毒治疗大肠癌的体外研究  

Gemcitabine Combined with Selective Oncolytic Adenovirus in Treatment of Colorectal Cancer: An in Vitro Studies

作　　者：渠红霞[1] 袁彩君[2] 王越[2] 

机构地区：[1]辽宁医学院研究生院肿瘤学专业,辽宁省锦州市121000 [2]辽宁医学院附属第一医院肿瘤科

出　　处：《中国全科医学》2013年第26期3088-3092,共5页Chinese General Practice

基　　金：辽宁省科学技术计划项目资助(2010010280-401)

摘　　要：目的探讨吉西他滨(Gem)联合E1B缺失溶瘤型腺病毒对大肠癌细胞体外的杀伤效果及安全性。方法体外培养大肠癌细胞系HCT-116及人脐静脉内皮细胞(HUVEC),重组腺病毒(Ad-GFP)感染细胞,根据加入的病毒和(或)药物分为:dl1520组、ZD55组、dl1520联合Gem组、ZD55联合Gem组、dl1520联合5-Fu组、ZD55联合5-Fu组、Gem组和5-Fu组。荧光显微镜观察病毒感染率,MTT法体外检测大肠癌细胞系的杀伤效果,普通倒置显微镜对肿瘤细胞的瘤裂解进行形态学观察,TCID50测定病毒滴度。结果感染复数(MOI)=100时,HCT-116和HUVEC对腺病毒的感染均较敏感,且细胞的感染率均达到90%以上。不同组HCT-116和HUVEC存活率比较,差异均有统计学意义〔F=18.546,P=0.000,95%CI(68.318,88.285);F=37.079,P=0.000,95%CI(81.618,92.737)〕。HCT-116和HUVEC dl1520联合Gem组和5-Fu组均可部分杀伤细胞,ZD55联合Gem组细胞杀伤效果略逊于dl1520联合Gem组,dl1520组和ZD55组中只可少部分杀伤细胞。MTT法检测显示,HCT-116中dl1520联合Gem组、ZD55联合Gem组分别比dl1520组、ZD55组病毒滴度降低约400倍、50倍,dl1520联合5-Fu组、ZD55联合5-Fu组较dl1520组、ZD55组降低不明显。结论 E1B缺失溶瘤型腺病毒与Gem联合对体外大肠癌细胞系的杀伤作用更加强大,且安全性更高。Objective To investigate the killing effect of gemcitabine （Gem） combined with oncolytic adenovirus in vitro on colorectal cancer and its safety. Methods HCT - 116 in eolorectal cancer cell line and HUVEC in normal human um- bilical cord vein endothelial cell line, Ad - GEP infected cells were cultured in vitro. According to join virus and or drug is di- vided into： d11520 group, ZD55 group, d11520 with Gem group, ZD55 with Gem group, d11520 with 5 - Fu group, ZD55 with 5 - Fu group, Gem group and 5 - Fu group. Virus infection rate was detected with fluorescence microscopy, killing effect in colorectal cancer cell line by MTr method, tumor cell lysis observed morphologically with inverted microscope, virus titer by TCIDs0 method. Results When multiplicity of infection （MOI） = 100, HCT - 116 in colorectal cancer cell line and HUVEC in normal line were sensitive to adenovirus infection with an infection rate of over 90%. There was significant difference in surviv- al rates of HCT - 116 and HUVEC cells between different groups F = 18. 546, P =0. 000, 95% CI （68. 318, 88. 285） ; F = 37. 079, P =0. 000, 95% CI （81. 618, 92. 737） 3. Part of ceils were killed in HCT - 116, HUVEC d11520 with Gem group and 5 - Fu group, the killing effect of ZD55 with Gem group was a little inferior to that of d11520 with Gem group, very few cells were killed in groups d11520 and ZD55. In HCT- 116 in colorectal cancer cell line, by MTI＂ assay, the virus titer was 400 times, 50 times lower in groups d11520 with Gem, ZD55 with Gem than in groups d11520, ZD55 ; virus titer was not remarkably lower in groups d11520 with 5 - Fu, ZD55 with 5 - Fu than in groups d11520, ZD55. Conclusion EIB - deleted mutants on- colytic adenovirus with Gem is of more powerful lethal effect on in vitro colorectal cancer cell line with a higher safety.

关 键 词：肠肿瘤 吉西他滨 腺病毒科 

分 类 号：R735.34[医药卫生—肿瘤]