B7联合HSV-TK基因对大鼠乳腺癌的治疗作用

Inhibitory effect of B7 in combination with HSV-TK on mammary cancer in rats

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 explain the effect of HSV TK and B7 combined injection on tumor size, animal survival time and cell immunogenicity. Methods: Eighty mammary cancer mice were equally divided into 4 groups: control, TK, B7,TK/B7. Two weeks later, the SHZ 88 cell transfered control vector: GcTKpSN,GcpB7SN and GcTKpB7SN were injected into the tumor directly and respectively. GCV was administered intraperitoneally at a dosage of 50 mg·kg -1 ·d -1 for 15 days. The tumor size and mass, survival time of the mice were documented. Results: Compared with control group, the tumor growth rate and tumor size were markedly lower and survival time were remarkably longer in TK and B7 group ( P <0.05), especially in TK/B7 group ( P <0.01). Conclusion: Combination of B7 and TK can not only suppress tumor growth, prolong animal survival time, but also enhance immunogenicity.