单纯疱疹病毒胸苷激酶和B细胞活化抗原联合基因治疗乳腺癌

A combination of herpes simplex virus thymidine kinase and costimulatory molecule B7 treament on murine mammary cancer

目的 观察逆转录病毒介导的单纯疱疹病毒胸苷激酶基因 (HSV TK)、B细胞活化抗原 (B7)基因联合瘤体内直接注射对荷瘤动物瘤体大小、重量、生存期以及全身细胞免疫功能的影响。方法 建立乳腺癌SHZ 88细胞株的动物模型 ,随机分为对照组、胸苷激酶基因组、B7组及TK +B7组 ,每组 30只。 2周后瘤体内分别注射转染有空壳载体及不同重组的GcTKpSN、GcB7pSN和GcTKpB7SN基因载体的乳腺癌细胞 ,并按 5 0mg·kg-1·d-1腹腔内注射羟甲基无环鸟苷 (GCV)治疗15d ,观察对肿瘤体积、重量及荷瘤生存时间的影响 ,4h51Cr释放法检测荷瘤小鼠脾细胞毒T淋巴细胞 (CTL)活性。结果 TK、B7组肿瘤生长速度减缓 ,重量减轻 ,荷瘤生存期TK组为 (6 8.88± 4.0 9)d ,B7组为 (6 8.75± 5 .14)d (P <0 .0 5 ) ,TK +B7组尤为显著 ,为 (97.38± 11.31)d (P <0 .0 1)。脾细胞CTL活性B7组为 (6 7.4± 4.3) % ,TK +B7组为 (6 2 .1± 3 .5 ) %较对照组、TK相比明显增强 (P<0 .0 1)。结论 HSV TK、B7基因联合组瘤体内注射不仅能抑制肿瘤的生长 ,延长荷瘤动物的生存期 ,而且具有增强机体免疫力的作用。

Objective\ To explore the influence on tumor size,weight, animal survival time and cell immanoglnicity of direct tumor injection of both HSV TK and B7. Methods\ 120 mammary cancer mice were equally divided into four groups: control, TK, B7, TK+B7. Two weeks later, control vector,GcTKpSN, GcBTpSN and GcTKpB7SN were injected into the tumor directively and respectively, GCV was administed intraperitoneally with a dosage of 50 mg·kg -1 ·d -1 for 15 days .The tumor size and weight, tumor bearing mice survival time were documented, CTL activity of spleen cell were determined by 4 h 51 Cr releasing method. Results\ Compared with control group ,the tumor growth rate and tumor weight were markedly lower and survival time remarkbly longer in TK group (68.88±4.09) d , B7 group (68.75± 5.14 ) d ( P <0.05),especially in TK+B7 group (97.38±11.31) d ( P <0.01).CTL activity in B7 group (67.4±4.3)% and TK+B7 group (62.1±3.5)% was significantly higher than those in control group and TK group ( P <0.01). Conclusion\ The therapy system of combination of B7 and TK can not only suppress tummor growth,prolong animal survival time ,but also enhance immunogenicity.\;