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目的 :探讨逆转录病毒介导的单纯疱疹病毒胸苷激酶基因 (HSV- TK)和共同刺激因子 B7基因联合使用对乳腺癌动物模型的体内治疗作用。方法 :应用基因重组技术 ,构建分别携带 HSV- TK,B7及 HSV- TK/B7双基因的逆转录病毒载体。以 SHZ- 88细胞株建立乳腺癌动物模型 ,随机分为对照组、TK组、B7组及 TK/B7组 ,每组 2 0只。 2周后于瘤体内分别注射转染有空载体及不同的重组载体的乳腺癌细胞 ,3d后于腹腔内连续注射无环鸟苷 (GCV) 15 d(5 0 mg· kg- 1· d- 1 ) ,观察肿瘤体积、荷瘤生存时间的变化和组织病理改变。结果 :B7组、TK/B7组肿瘤内淋巴细胞浸润明显增多。与对照组相比 ,TK组、B7组肿瘤生长减缓 ,体积减小 ,荷瘤生存期延长 ,两组间均有显著差异 (P<0 .0 5 ) ,而 TK /B7组尤为显著 (P<0 .0 1) ;TK组与 B7组相比则无显著差异。 结论 :HSV- TK,B7基因联合治疗乳腺癌动物模型 ,能直接杀伤肿瘤 ,抑制肿瘤生长 ,延长荷瘤动物的生存期。
Objective: To investigate the in vivo therapeutic effects of retrovirus-mediated herpes simplex virus thymidine kinase gene (HSV-TK) and costimulatory factor B7 gene combination on breast cancer animal models. METHODS: Gene recombination technology was used to construct retroviral vectors carrying HSV-TK, B7 and HSV-TK/B7 double genes. The animal model of breast cancer was established with SHZ-88 cell line and randomly divided into control group, TK group, B7 group and TK/B7 group with 20 rats in each group. Two weeks later, breast cancer cells transfected with empty vector and different recombinant vectors were injected into the tumor body. After 3 days, acyclovir (GCV) was continuously injected intraperitoneally for 15 days (50 mg·kg-1 ·d- 1) Observe changes in tumor volume, tumor survival time, and histopathological changes. Results: Intratumoral lymphocyte infiltration in B7 and TK/B7 groups increased significantly. Compared with the control group, tumors in the TK group and the B7 group had slower growth, smaller volume, and longer tumor-bearing survival time. There was a significant difference between the two groups (P<0.05), and the TK/B7 group was particularly significant (P<0.05). <0. 0 1); There was no significant difference between the TK group and the B7 group. Conclusion: HSV-TK and B7 gene combination therapy for breast cancer animal models can directly kill tumors, inhibit tumor growth, and prolong the survival period of tumor-bearing animals.