Gene target therapy against human bladder cancer by gelsolin gene

我们构建并测试了重组腺病毒编码野生型gelsolin (Ad-GSN)，以确定gelsolin过表达作为治疗试剂在裸鼠原位模型中的有效性。该模型提供了一个类似于术后膀胱癌的微环境。体外实验证实了Ad-GSN对人膀胱癌细胞株KU-7的生长有抑制作用。流式细胞术分析显示，这种影响可能发生在G2/M时细胞周期阻滞或延迟。将KU-7细胞导入裸鼠膀胱，经尿道注射Ad-GSN或对照腺病毒1×10^9 PFU 3 d。10天后，染色后数字化测定各膀胱20个切片肿瘤肿块总面积。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，利用腺病毒载体表达凝胶蛋白可能是一种有效的膀胱癌治疗试剂。

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.