Gene target therapy against human bladder cancer by gelsolin gene

凝溶胶蛋白基因针对人膀胱癌的基因靶向治疗

• 批准号: 11557187
• 负责人: KUZUMAKI Noboru
• 金额: $ 3.84万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557187/
• 关键词: gelsolin; bladder cancer; gene therapy; adenovirus; nude mice; β-gal

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.

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。

项目成果

Watanabe T.: "An improved intravesical model using human bladder cancer cell lines to optimize gene and other therapies."Cancer Gene Therapy. 7. 1575-1580 (2000)

Watanabe T.：“一种改进的膀胱内模型，使用人类膀胱癌细胞系来优化基因和其他疗法。”癌症基因疗法。

Banno, Y.: "Differential phospholipase D activation by btadykinin and sphingosine 1-phosphate in NIH 3T3 fibroblasts overexpress gelsolin"J. of Biological Chemistry. 274. 27385-27391 (1999)

Banno, Y.：“NIH 3T3 成纤维细胞过度表达凝溶胶蛋白，通过缓激肽和 1-磷酸鞘氨醇激活不同的磷脂酶 D”。

Tanaka, M.: "Gelsolin gene therapy by retrovirus producer cells for human bladder cancer in nude mice"Cancer Gene Therapy. 6. 482-487 (1999)

Tanaka, M.：“逆转录病毒生产细胞对裸鼠人膀胱癌进行凝溶胶蛋白基因治疗”癌症基因治疗。

Sakai, N.: "Enhancement of G2 checkpoint function by gelsolin in human cancer"Exp. Cell Res.. 251. 224-233 (1999)

Sakai, N.：“人类癌症中凝溶胶蛋白增强 G2 检查点功能”实验。

Banno, Y.: "Differential phospholipase D activation by btadykinin and sphingosine 1-phosphate in NIH 3T3 fibroblasts overexpressing gelsolin"J. of Biological Chemistry. 274. 27385-27391 (1999)

Banno, Y.：“在过度表达凝溶胶蛋白的 NIH 3T3 成纤维细胞中，缓激肽和 1-磷酸鞘氨醇对磷脂酶 D 的激活作用不同”J.