逆转录病毒介导HSV-TK基因治疗膀胱癌及旁观者效应的观察

Retroviral-mediated HSV-tk gene therapy on bladder cancer ex vivo and its bystander effect

目的 观察HSV TK/GCV治疗膀胱癌的体内效果及旁观者效应。方法 用逆转录病毒感染鼠源性膀胱癌细胞T739,以不同比例的T739和T739TK细胞建立膀胱癌腹腔肿瘤模型 ,同时 ,在背部皮下以母代细胞T739建立皮下肿瘤 ,观察GCV治疗前后肿瘤大小变化及动物存活时间。结果 动物存活时间随基因转移效率提高而延长 ,腹腔肿瘤生长受到抑制 ,背部肿瘤在 5 0 %以上转移效率时肿瘤生长缓慢。结论 HSV TK/GCV对膀胱癌的体内杀伤效应随基因转移效率提高 ,并存在远距离旁观者效应。

Objective To observe the effects of hsv tk/gcv system on bladder cancer and its bystander effect by ex vivo. Methods HSV TK gene was transferred into urine bladder cancer cell line T739 by retrovirus in vitro. Tumors were induced in syngeneic mice by peritoneum injection with different ratio of T739 and T739TK cells. At the same time, subcutaneous tumors in back were established with parent T739 cells. After 6 days administration of GCV tumor volume and survival time were investigated. Result Tumor growth was inhibited and mice survival time prolonged with higher TK gene transfer ratio, when the ratio was above 50% subcutaneous tumor growth was also inhibited significantly. Conclusion The effects of hsv tk/gcv on bladder cancer is enhanced by higher gene transfer ratio and the distant bystander effect is found.