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人内皮抑素的抗血管生成活性抑制膀胱癌生长及其机制。

The anti-angiogenic activity of human endostatin inhibits bladder cancer growth and its mechanism.

作者信息

Du Zhijun, Hou Shukun

机构信息

Department of Urology, Peking University People's Hospital, Peking, People's Republic of China.

出版信息

J Urol. 2003 Nov;170(5):2000-3. doi: 10.1097/01.ju.0000091879.18156.22.

DOI:10.1097/01.ju.0000091879.18156.22
PMID:14532841
Abstract

PURPOSE

We investigated whether recombinant human endostatin can inhibit the growth of bladder cancer in an experimental model and its possible mechanism of action.

MATERIALS AND METHODS

The recombinant human endostatin protein was induced and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot assays. Its biological activities and the possible mechanisms of action were studied in vitro and in vivo.

RESULTS

Recombinant human endostatin inhibited the proliferation of endothelial cells (ECV304) but not bladder tumor cells (EJ). Endostatin induced the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in bladder cancer cells. Endostatin slowed the growth of xenograft bladder tumors. Immunohistochemistry revealed that endostatin blocked angiogenesis by decreasing vascular endothelial growth factor expression and inducing apoptosis in bladder cancer cells.

CONCLUSIONS

These findings demonstrate that endostatin can inhibit xenograft bladder cancer growth and this effect is likely to be mediated by regulating matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and vascular endothelial growth factor expression, and by inducing apoptosis.

摘要

目的

我们研究了重组人内皮抑素在实验模型中是否能抑制膀胱癌生长及其可能的作用机制。

材料与方法

重组人内皮抑素蛋白经十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳和蛋白质印迹分析诱导并确认。在体外和体内研究其生物学活性及可能的作用机制。

结果

重组人内皮抑素抑制内皮细胞(ECV304)增殖,但不抑制膀胱肿瘤细胞(EJ)增殖。内皮抑素诱导膀胱癌细胞中基质金属蛋白酶及其组织抑制剂的表达。内皮抑素减缓了异种移植膀胱肿瘤的生长。免疫组织化学显示,内皮抑素通过降低血管内皮生长因子表达和诱导膀胱癌细胞凋亡来阻断血管生成。

结论

这些发现表明内皮抑素可抑制异种移植膀胱癌的生长,且这种作用可能是通过调节基质金属蛋白酶、基质金属蛋白酶组织抑制剂和血管内皮生长因子的表达以及诱导凋亡来介导的。

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