TSA联合基因工程腺病毒H101治疗食管癌皮下移植瘤的研究  

TSA Combined with Genetically Engineered Adenovirus H101 in the Treatment of Tumor Tissues Transplanted with Esophageal Cancer Cells

作　　者：冯婷[1] 刘霞[2] 马俊芬[3] 杨红艳[3] 李沛[3] 董子明[3] 

机构地区：[1]郑州大学护理学院,河南郑州450052 [2]徐州医学院附属第三医院,江苏徐州221000 [3]郑州大学基础医学院病理生理学教研室,河南郑州450052

出　　处：《肿瘤基础与临床》2011年第5期369-373,共5页journal of basic and clinical oncology

摘　　要：目的研究曲古霉素A(TSA)对基因工程腺病毒H101杀伤食管癌EC9706细胞作用的影响,探讨HDAC抑制剂在腺病毒载体基因治疗中应用的可能性和作用机制。方法 1)先成瘤后治疗组,构建裸鼠食管癌移植瘤模型,待肿瘤长至肉眼可见的肿块(约8 mm×7 mm)后分组。TSA治疗组:每只每次瘤内注射1.0μmol/L TSA;H101治疗组:瘤内注射50×108vp/d H101;TSA联合H101治疗组:即先注射TSA,第2天注射H101,注射剂量同上。另设空白对照组,以上治疗持续2周,治疗结束取瘤组织检测;2)先处理后成瘤组:分别采用浓度为4.0μmol/L TSA体外处理EC9706细胞48 h,浓度200×108vp/d H101处理EC9706细胞48 h及两者联合处理EC9706细胞48 h,同样设置不做处理的空白对照组,将处理后的细胞种植于裸鼠左上肢腋下构建裸鼠食管癌移植瘤模型。待肿瘤长至肉眼可见的肿块(约8 mm×7 mm)后,取瘤组织用RT-PCR、W estern b lot和免疫组化法检测柯萨奇-腺病毒受体(CAR)在移植瘤中的表达,测量肿瘤体积。结果无论是先处理后成瘤组还是先成瘤后治疗组,TSA组和TSA联合H101组均可上调裸鼠食管癌移植瘤组织中CAR蛋白的表达,与空白对照组和H101组比较差异均有统计学意义(P<0.05),但TSA组和TSA联合H101组之间比较差异无统计学意义(P>0.05)。而TSA联合H101组对人食管癌EC9706细胞裸鼠皮下移植瘤大小影响与TSA、H101组比较差异均有统计学意义(P<0.05),TSA与H101组比较差异无统计学意义(P>0.05)。各治疗组与空白对照组比较差异均有统计学意义(P<0.05)。结论 TSA能增强H101治疗人食管癌裸鼠皮下移植瘤,其作用机制之一是TSA上调了食管癌CAR蛋白的表达。Objective To observe the influence of TSA of effect of genetic engineering adenovirus H101 killing esophageal cancer EC9706 cells,and to discuss the action mechanisms and the possible applications of HDAC inhibitors in adenovirus vectors for gene therapy.Methods 1） The first examination was treatment after growing tumor.the examination following was building nude model of transplanted tumor in esophageal cancer,and were divided when the tumor growing visible masses in the tumor grew to 8 mm×7 mm,the TSA treatment group（Intratumoral injection TSA 1.0 μmol/L TSA/time）;the H101 treatment group（Intratumoral injection H101 50×108 vp/d）;the TSA and H101 treatment group,the first to inject TSA,and the next day to inject H101,the injection dosage as above.Another group was the blank control group.The tumor tissues were obtained after treating two weeks;2） the section examination was treatment before growing tumor.one group was utilizing the concentration of 4.0 μmol/L TSA to treat EC9706 cells for 48 h,the second group was utilizing the concentration of 200×108 vp/d H101 to treat EC9706 cells for 48 h,the third group was using the two drugs to treat EC9706 cells for 48 h,another group was matched group.The treated cells grown under skin of nude mice to built xenograft model of esophageal cancer.After the tumor growing visible masses in the tumor grew to 8 mm×7 mm,the tumor tissues were obtained,and RT-PCR,Western blot and immunohistochemistry were used to detect the expression of CAR in the tumors and measure tumor volume.Results Whether the first examination of tumor or the section examination,compared with the matched group and the H101 treatment group,the TSA treatment group and the TSA and H101 treatment group were able to rise the expressions of CAR protein in esophageal cancer xenograft tissues in nude mice（P〈0.05）.But the TSA group and the TSA and H101 treatment group were no significant difference（P〉0.05）.But the TSA and H101 treatment group to the human esophageal cancer EC9706 cell

关 键 词：柯萨奇-腺病毒受体 曲古菌素A 基因工程腺病毒 EC9706 裸鼠 

分 类 号：R735.1[医药卫生—肿瘤] R730.231[医药卫生—临床医学]