论文部分内容阅读
目的：探讨重组腺病毒介导胸苷激酶系统通过血管靶向治疗裸鼠皮下人肝癌细胞移植瘤的疗效及作用机制。方法：32只BALB/c鼠皮下接种建立裸鼠皮下人肝癌细胞移植瘤模型,当瘤体达100 mm~3时随机分成4组,分别为更昔洛韦(GCV)组(Ⅰ)、空载体病毒组(Ⅱ)、重组腺病毒CMV-TK组(Ⅲ)及重组腺病毒AdKDR-TK组(Ⅳ)。各治疗组瘤内分别注入重组腺病毒液及空载体病毒液,重组腺病毒治疗组在病毒给予24 h后分别在腹腔内注射GcV,连续10 d；对照组腹腔内注入GCV。观察各组瘤体生长情况及免疫组化法测定肿瘤微血管密度(MVD)。结果：与对照组比较,第Ⅲ、Ⅳ组经治疗后肿瘤的生长均受到了明显的抑制,其抑瘤率分别为12．3%和24．5%(两者比较,P＜0．05)。肿瘤组织内的MVD,Ⅰ组为(37．4±8．6)个/mm~2、Ⅱ组为(30．6±7．8)个/mm~2、Ⅲ组为(27．6±7．1)个/mm~2、Ⅳ组为(10．7±4．1)个/mm~2,其中Ⅲ组与Ⅱ组(P＜0．05)、Ⅳ组与Ⅱ组(P＜0．01)、Ⅳ组与Ⅲ组(P＜0．01)之间的肿瘤内MVD比较均有统计学差异。结论：重组腺病毒介导以KDR为启动子的胸苷激酶系统能够通过血管靶向性地有效抑制肿瘤的生长。
Objective: To investigate the therapeutic effect and mechanism of recombinant adenovirus mediated thymidine kinase system targeting transplanted tumor of subcutaneous human hepatocellular carcinoma in nude mice by vascular targeting. METHODS: Twenty-two BALB / c mice were inoculated subcutaneously to establish a subcutaneous human hepatoma cell xenograft model in nude mice. When the tumor size reached 100 mm ~ 3, the mice were randomly divided into 4 groups: ganciclovir (GCV) group (Ⅱ), recombinant adenovirus CMV-TK group (Ⅲ) and recombinant adenovirus AdKDR-TK group (Ⅳ). Each treatment group were injected with recombinant adenovirus vector and empty vector virus, the recombinant adenovirus treatment group were injected with GcV intraperitoneally for 24 hours after the virus was given for 10 days, and the control group was intraperitoneally injected with GCV. The growth of tumor in each group was observed and the tumor microvessel density (MVD) was measured by immunohistochemistry. Results: Compared with the control group, the growth of tumors in group Ⅲ and group Ⅳ were significantly inhibited, and the tumor inhibition rates were 12.3% and 24.5% respectively (P <0.05 ). MVD in groupⅠwas (37.4 ± 8.6) / mm ~ 2, group Ⅱ was (30.6 ± 7.8) / mm ~ 2, group Ⅲ was (27.6 ± 7.1) / mm ~ 2, and (10.7 ± 4.1) / mm ~ 2 in group Ⅳ, with group Ⅲ and group Ⅱ (P <0.05), group Ⅳ and group Ⅱ (P < 0.01). There was significant difference in MVD between group Ⅳ and group Ⅲ (P <0.01). CONCLUSION: The recombinant adenovirus mediated KDR-mediated thymidine kinase system can effectively inhibit tumor growth through vascular targeting.