HSV—TK、B7联合基因治疗乳腺癌的动物实验研究

A COMBINATION OF B7 AND HSV-TK 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、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 explone the influence on tumor size、weight、animal survival time and cell immanoglnicity of direct tu-mor injection of both HSV-TK and BT.Method 120mammary cancer mice were equally divided into four groups:control、TK、B7、TK+B7.Two weeks later,control vector、GcTKpSN,pB7SN and GeTKpB7SNwere injected into thd tumor directively and respective-ly,GCV was admiristed intraperitoncally with a desage of 50mg.kg^(-1).d^(-1) for 15 days.The tumor size and weight、tumor mice survivaltime were documented,CTL activity of spleen cell were determined by 4 hours'^(51) Cr releasing method.Result Compared with controlgroup,the tumor growth rate and tumor weight were markedly lower and survival time remarkbly longer in TE and B7 group(P<0.05),especially in TK+B7 group(P<0.01).CTL activity in group conteol and group TK+B7 was significantly higher than those ingroup control and group TK(P<0.01).Conclusion The therapy system of combination of B7 and TK can not only suppress tumorgrowth,prolong animal survival time,but also enhance immunogenicity.