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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、TK组、B7组及TK+B7组,每组30只。二周后瘤体内分别注射转染有空壳载体及不同重组的Gc-TKpSN、GcB7pSN和GcTKpB7SN 基因载体的乳腺癌细胞,并按50mg·kg~(-1)·d~(-1)腹腔内注射羟甲基无环鸟苷(GCV)治疗15天,观察对肿瘤体积、重量及荷瘤生存时间的影响,4小时~(51)Cr法释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,荷瘤生存期延长(P<0.05),TK+B7组尤为显著(P<0.01)。B7、TK+B7两组脾细胞CTL活性较对照组、TK相比明显增强(P<0.01)。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作用。
Objective To observe the effect of retrovirus-mediated herpes simplex virus thymidine kinase gene (HSV-TK) and B cell activating antigen (B7) gene injection in vivo on the tumor size, weight, survival, Impact of immune function. Methods The animal model of SHZ-88 breast cancer cell line was established and randomly divided into control group, TK group, B7 group and TK + B7 group, with 30 in each group. Two weeks later, the breast cancer cells were transfected with the empty vector and the recombinant Gc-TKpSN, GcB7pSN and GcTKpB7SN vector respectively, and then injected into the abdominal cavity at a dose of 50mg · kg -1 · d -1 The effect of injection of GCV on the tumor volume and weight and tumor-bearing survival time was observed for 15 days. The spleen cytotoxic T lymphocytes (CTL) activity. Results The tumor growth rate of TK and B7 group was slowed down, the weight was reduced, the tumor-bearing survival was prolonged (P <0.05), especially in TK + B7 group (P <0.01). The CTL activity of splenocytes in B7 and TK + B7 groups was significantly higher than that in control group and TK (P <0.01). Conclusion In vivo injection of HSV-TK and B7 gene combination therapy can not only inhibit tumor growth, prolong the survival of tumor-bearing animals, but also enhance the body immunity.