hTERT启动子调控的CD:UPRT/5-FC自杀基因对人胃癌裸鼠移植瘤的抑制作用  

Inhibitory effects of CD:UPRT/5-FC suicide gene under control of hTERT promoter on human gastric cancer xenograft in nude mice

作　　者：曹伟军[1] 张振玉[1] 张桂英[2] 

机构地区：[1]南京医科大学附属南京第一医院消化内科,江苏南京210006 [2]中南大学湘雅医院消化内科,湖南长沙410008

出　　处：《现代肿瘤医学》2010年第5期872-875,共4页Journal of Modern Oncology

摘　　要：目的:研究人端粒酶逆转录酶(hTERT)启动子调控的胞嘧啶脱氨酶:尿嘧啶磷酸核糖转移酶/5-氟胞嘧啶(CD:UPRT/5-FC)融合自杀基因系统在体内对人胃癌SGC7901细胞的杀伤作用。方法:构建胃癌皮下移植瘤模型,随机分成3组处理。观察30天,测量肿瘤体积,计算抑瘤率。肿瘤组织做常规病理检查,免疫组化检测CD蛋白的表达。结果:成功构建胃癌皮下移植瘤模型。治疗30天后,B组(瘤内注射hTERT-CD:UPRT+腹腔注射PBS)和C组(单纯腹腔注射PBS)的肿瘤生长迅速,肿瘤体积分别为(2.72±0.35)cm3、(2.67±0.30)cm3,A组(瘤内注射hTERT-CD:UPRT+腹腔注射5-FC)的肿瘤生长受到明显抑制,第30天体积为(1.10±0.13)cm3,与前两组相比差异有统计学意义(P<0.05),其抑瘤率为59.6%。裸鼠移植瘤病理切片镜检,A组可见大量肿瘤细胞排列稀疏,部分肿瘤细胞核固缩、核碎裂;B组和C组则见大量肿瘤细胞排列紧密,细胞形态和细胞核呈多形性,核大深染,核分裂像多见。免疫组化显示,A组和B组可见CD的表达,C组CD表达呈阴性。结论:hTERT启动子调控的CD:UPRT/5-FC融合自杀基因系统对裸鼠胃癌皮下移植瘤有显著的杀伤作用,为胃癌的基因治疗提供了一种可能的方法。Objective： To investigate the inhibitory effects of CD ： UPRT/5 - FC （ cytosine deaminsae ： uracil phos- phoribosyhransferase/5 - flurocytosine） under control of hTERT promoter on human gastric cancer cells SGC7901 in vivo. Methods：Mice models bearing subcutaneous tumors of SGC7901 cells were established and divided into three groups. After 30 days,all mice were sacrificed and tumors were excised for routine histological examination and immu- nohistochemical staining of CD. Results：Mice models bearing subcutaneous tumors of SGC7901 cells were established successfully. After 30 days of treatments, the tumors of Group B （ hTERT - CD ： UPRT ＋ PBS） and Group C （PBS） grew rapidly and the volumes were （2.72 ± 0.35 ）cm3 and （2.67±0.30）cm3, respectively. But the tumors of Group A （ hTERT - CD ： UPRT ＋ 5 - FC） were retarded significantly and the volume was （ 1.10 ± 0.13 ） cm3 （ P 〈 0.05 ）. The growth inhibition ratio was 59.6%. Histological examination showed that in group A, tumor cells were packed sparsely and nuclear condensation and fragmentation can be observed. In group B and C, tumor cells were packed tightly and nuclear pleomorphism, hyperchromasia and mitotic figure were occasionally observed. Analyzed by immuno- histochemical staining, the expression of CD was positive in group A and B, but negative in group C. Conclusion：CD： UPRT/5 - FC under control of hTERT promoter can kill SGC7901 cells in vivo and is a promising method for gastric cancer gene therapy.

关 键 词：胞嘧啶脱氨酶:尿嘧啶磷酸核糖转移酶 人端粒酶逆转录酶启动子 胃癌 基因治疗 

分 类 号：R730.5[医药卫生—肿瘤] R735.2[医药卫生—临床医学]