Gene target therapy against human bladder cancer by gelsolin gene

我们发起并测试了编码野生型明胶蛋白的重组腺病毒(Ad-GSN)，以确定明胶蛋白过表达作为治疗试剂在裸鼠原位模型中的疗效。这个模型提供了一个类似于膀胱癌术后的微环境。体外实验证实，Ad-GSN对人膀胱癌KU-7细胞的生长有抑制作用。流式细胞仪分析表明，这种作用可能与细胞周期停滞或延迟于G2/M期有关。在该原位模型中，将KU-7细胞导入裸鼠膀胱，经尿路注射1×109pfu的Ad-GSN或对照组腺病毒3d。10d后，染色后数字化测定每个膀胱20个切片的肿块总面积。在Ad-GSN治疗的膀胱中，与对照组相比，大约90%的肿瘤生长受到抑制。这些结果提示，用腺病毒载体表达明胶蛋白有可能作为膀胱癌的治疗试剂。

We originated and tested recombinant adenovirus encoding wild-type gelsolin (Ad-GSN) to determine the efficacy of gelsolin overexpression as a therapeutic reagent in an orthotopic model of nude mice. This model provides a microenvironment similar to that of postsurgical bladder cancer. In vitro, an inhibitory effect on the growth of human bladder cancer cell line KU-7 infected with Ad-GSN was confirmed. Flow cytometric analysis revealed this effect may be occurred by cell cycle arrest or delay at G2/M.In this orthotopic model, KU-7 cells were introduced into the bladder of nude mice, and 1×10^9 PFU of Ad-GSN or control adenovirus was injected via the urethra for three days. After 10 days the total area of tumor masses in 20 sections of each bladder was digitally determined after staining. In Ad-GSN treated bladder, approximately 90% of tumor growth was inhibited compared to controls. These findings suggest that the expression of gelsolin using adenovirus vector may be useful as a therapeutic reagent against bladder cancer.