ABSTRACT

Bladder cancer is a common and widespread cancer of the human urinary system, and its incidence is increasing. Gene therapy is a promising treatment of bladder cancer. In our study, a recombinant adeno-associated virus (rAAV9-UPII-TK-EGFP) driven by a UPII promoter was constructed. The efficacy and safety of infection of bladder cells was tested in vivo and in vitro. The ability of rAAV9-UPII-TK-EGFP to penetrate the glycosaminoglycan (GAG) layer on the surface of bladder cells and to transduce the bladder cells in vivo was very high. Additionally, we confirmed that the TK/GCV system has a powerful cytotoxic effect on bladder tumor cells in vitro and in vivo. Thus, our data indicate that rAAV9-UPII-TK-EGFP is a precise gene drug delivery system for the treatment of bladder cancer, and the TK/GCV therapeutic strategy has a powerful antitumor effect. These findings can be widely used in clinical and scientific studies.

摘要

膀胱癌是人类泌尿系统常见且广泛的癌症，其发病率呈上升趋势。基因治疗是一种很有前景的膀胱癌治疗方法。在我们的研究中，构建了由 UPII 启动子驱动的重组腺相关病毒 (rAAV9-UPII-TK-EGFP)。在体内和体外测试了膀胱细胞感染的有效性和安全性。rAAV9-UPII-TK-EGFP 穿透膀胱细胞表面的糖胺聚糖 (GAG) 层并在体内转导膀胱细胞的能力非常高。此外，我们证实 TK/GCV 系统在体外和体内对膀胱肿瘤细胞具有强大的细胞毒作用。因此，我们的数据表明，rAAV9-UPII-TK-EGFP 是一种用于治疗膀胱癌的精确基因药物递送系统，并且 TK/GCV 治疗策略具有强大的抗肿瘤作用。