巨细胞病毒嵌合癌胚抗原介导单纯疱疹病毒胸苷激酶联合丙氧鸟苷自杀基因体系靶向性治疗结肠癌的效果

摘要

Objective To approach the treatment efficiency of replication defective adenovirus carrying HSV/TK gene under control of the cytomegalovirus union carcinoembryonic antigen promoter and ganciclovir (GCV) in nude mice xenografts model of human colon cancer. Methods The model of human colon cancer xenografts in BALB/c nude mouse was builded successfully. After injection of different concentration gradient of Ad-CMV-CEA-HSV/TK (1.0í109/kg, 5.0í109/kg, 10.0í109/kg) in caudal vena, the same level of GCV (50 mg/kg) was given by peritoneal injection, and they were divided into the blank control group and Ad-CEA-HSV/TK control group with different concentration (1.0í109/kg, 5.0í109/kg, 10.0í109/kg) were set, in total of 7 groups, each group of 10 mice. The anti-tumor efficacy was analyzed by index of tumor volume, tumor weight, relative tumor curative, and tumor growth curve. Results After therapy, growth of human colon cancer xenografts in nude mouse were observably inhibited by Ad-CMV-CEA-HSV/TK/GCV and Ad-CEA-HSV/TK/GCV in a dose dependent, and there were no inhibition plateau. Ad-CMV-CEA-HSV/TK/GCV showed a stronger inhibition ability than Ad-CEA-HSV/TK/GCV (P<0.05). Conclusion Ad-CMV-CEA-HSV/TK/GCV system is highly experimental effective and safe to inhibit the growth of human colon cancer xenografts, provides scientific ba-sis forⅠ period experimental of clinical treatment of human colon cancer and colon cancer distant metastases, and has a wide prospect of clinical application.%目的：观察巨细胞病毒(CMV)嵌合以癌胚抗原为启动子，以腺病毒为载体的单纯疱疹病毒胸苷激酶基因重组构建体Ad-CMV-CEA-HSV/TK联合丙氧鸟苷(GCV)体内抗结肠癌的疗效。方法构建人结肠癌裸鼠移植瘤模型，按不同浓度梯度Ad-CMV-CEA-HSV/TK(1.0×109/kg、5.0×109/kg、10.0×109/kg)经尾静脉注射带瘤小鼠后，腹腔注射相同浓度GCV(50 mg/kg)，并设空白对照组及不同浓度的Ad-CEA-HSV/TK/GCV对照(1.0×109/kg、5.0×109/kg、10.0×109/kg)，共设A~G 7组，每组各10只小鼠。观察肿瘤体积、重量、肿瘤体积-时间曲线、肿瘤抑制率及生存期。结果 Ad-CMV-CEA-HSV/TK/GCV及Ad-CEA-HSV/TK/GCV对人结肠癌裸鼠移植瘤生长均具有抑制作用，对移植瘤的体积及重量抑制呈作用物浓度依赖性；且Ad-CMV-CEA-HSV/TK/GCV抑制能力较Ad-CEA-HSV/TK/GCV显著，差异有统计学意义(P<0.05)。结论 Ad-CMV-CEA-HSV/TK/GCV体系对结肠癌具有明确的实验性治疗作用，为人结肠癌及结肠癌远处转移灶的Ⅰ期临床治疗试验提供科学实验依据，具有广阔的临床应用前景。