胸苷激酶／更昔洛韦系统联合肿瘤坏死因子-α治疗鼠膀胱癌  

Thymidine kinase/ganciclovir therapy in combination with tumor necrosis factor-or for murine bladder cancer

作　　者：石向华[1] 谭万龙[2] 李民[1] 杜跃军[2] 梁中锟[2] 

机构地区：[1]南方医科大学珠江医院器官移植科,广州510282 [2]南方医科大学南方医院泌尿外科

出　　处：《中华实验外科杂志》2012年第6期1006-1008,共3页Chinese Journal of Experimental Surgery

基　　金：基金项目：广东省自然科学基金资助项目（020059）

摘　　要：目的观察腺病毒介导胸苷激酗更昔洛韦（TK／GCV）系统联合肿瘤坏死因子-a（TNF-a）对鼠膀胱癌的杀伤作用。方法构建MB49小鼠皮下模型，随机分为对照组、TK／GCV组、TNF-a组、联合治疗组。按治疗计划分组进行病毒及药物注射，实验结束测量肿瘤体积大小，进行组织病理学检查。结果体外实验验证低浓度TNF-a联合GCV较单纯GCV对细胞的杀伤率明显增强，差异有统计学意义（P〈0．01）。流式细胞仪检测，联合治疗组较单独用药组凋亡率明显提高，差异有统计学意义（P〈0．01）。动物实验结柬后肿瘤体积对比：TK／GCV组为（93．43±2．10）mm3、TNF-a组为（53．95±2．61）mm3、对照组为（171．52±4．33）mm3、联合治疗组为（18．23±1．11）mm3，联合治疗组肿瘤体积较其他各组明显缩小，差异有统计学意义（P〈0．01）。苏木素-伊红（HE）染色见各治疗组均出现细胞坏死凋亡，其中联合治疗组仅于周边见少量肿瘤细胞存活。结论GCV对转染腺病毒MB49细胞及TNF-a对MB49细胞均有良好的抑制生长作用，且呈浓度依赖性；TK／GCV、TNF-a均能有效诱导凋亡，且两者具有协同作用；TK／GCV系统联合小剂量TNF—a能增强自杀基因系统对小鼠膀胱癌的治疗作用。Objective To investigate the killing effect of adenovirus-mediated thymidine kinase/ ganciclovir （TK/GCV） gene therapy in combination with tumor necrosis factor-a （TNF-a） for murine bladder carcinoma ceils. Methods The animal models were established, and divided into 4 groups randomly： control, TNF-a injected subcutaneously around the tumor, GCV injected intraperitioneally, TNF-a injected subcutaneously around the tumor ＋ GCV injected intraperitioneally. The adenovirus and the drugs were injected as planned. During the course of the treatment, the volume of the tumors was measured. The tumor tissues were analyzed histopathologically. Results The survival rate of GCV on adenovirus-transfected MB49 cells decreased gradually as the concentration increased. The survival rate of TNF-a on MB49 ceils decreased gradually as the concentration increased. When GCV in combination with low concentration of TNF-a were added, the killing rate of the infected murine bladder carcinoma cells in each group increased significantly （P 〈 0. 01 ）. We can detected the apoptotic peak of sub-G1 stage in group of TK/GCV alone ,TNF-a alone and TK/GCV in combination with TNF-a by flow cytometry. The apoptotic rate of the unification group increased significantly （P 〈 0. 01 ）. When animal experiment in vivo completed, the average tumor volume of TK/GCV treated group was （ 93.43 ± 2. 10 ） mm3 , and TNF-a treated group was （53.95 ± 2. 61 ）mm3 , While the average tumor volume of the control proup was （ 171.52 ± 4. 33 ） mm3. The average tumour volume of TK/GCV ＋ TNF-a treated group was （ 18.23 ± 1.11 ）mm3 , smaller than any others （P 〈 0. 01 ）. Through histopathology detection we can see all the therapy group emerged cell necrosis and apoptosis. There are few tumor cell survived in bouncary in pathological section of the affiliation group. Conclusion GCV can inhibit the MB49 cells infected with TK gene efficiently. TNF-ct can inhibit and kill the MB49 cells. There are dose-dependent relation. TK

关 键 词：胸苷激酶/更昔洛韦 肿瘤坏死因子-A 膀胱癌 脱噬作用 

分 类 号：R737.14[医药卫生—肿瘤]