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[重组人血管生成抑制肽tumstatin对裸鼠移植人卵巢癌生长和转移的抑制作用]

[Inhibitory effect of recombinant anti-angiogenic peptide of tumstatin on growth and metastasis of human ovarian cancer transplanted in nude mice].

作者信息

Zhang Guang-Mei, Sui Li-Hua, Jia Tong, Zhao Yu-Zhen, Fu Song-Bin, Liu Xing-Han, Yu Yan

机构信息

Department of Gynecology, The First Clinical College of Harbin Medical University, Harbin 150001, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2008 Mar;30(3):170-3.

PMID:18756929
Abstract

OBJECTIVE

To evaluate the anti-angiogenic activity of peptide 21 obtained by modification of tumstatin, and its inhibitory effect on the growth and metastasis of human ovarian cancer transplanted in nude mice.

METHODS

The peptide 21 was purified by affinity chromatography. Human ovarian cancer SKOV3 cells were inoculated in nude mice and the transplanted tumor was treated with the peptide 21 to observe the tumor growth and metastasis. The microvessel density (MVD) and immunohistochemical staining index of PCNA, VEGF and MMP-2 and TIMP-2 were performed to assess the inhibitory effect of the peptide 21.

RESULTS

In the nude mice at 21 days after peptide 21 treatment, the inhibition rate of tumor growth was 53.17%, the tumor microvessel density was significantly reduced (P <0.05), the expression of PCNA, VEGF and MMP-2 were significantly lower (P <0.01), and TIMP-2 expression was significantly higher (P <0.01) in comparison with that of control group.

CONCLUSION

The peptide 21 generated in this study has a significant anti-angiogenetic activity, showing significant inhibitory effect on the growth of human ovarian cancer transplanted in nude mice. The mechanism of its inhibitory action on ovarian cancer growth may be mediated by reduction of neovascularization and reduction of expression of angiogenetic factors.

摘要

目的

评估通过对tumstatin进行修饰获得的肽21的抗血管生成活性及其对裸鼠移植的人卵巢癌生长和转移的抑制作用。

方法

通过亲和层析纯化肽21。将人卵巢癌SKOV3细胞接种于裸鼠,用肽21处理移植瘤,观察肿瘤生长和转移情况。进行微血管密度(MVD)以及PCNA、VEGF、MMP-2和TIMP-2的免疫组化染色指数检测,以评估肽21的抑制作用。

结果

在肽21处理21天后的裸鼠中,肿瘤生长抑制率为53.17%,肿瘤微血管密度显著降低(P<0.05),PCNA、VEGF和MMP-2的表达显著降低(P<0.01),与对照组相比,TIMP-2表达显著升高(P<0.01)。

结论

本研究中产生的肽21具有显著的抗血管生成活性,对裸鼠移植的人卵巢癌生长显示出显著的抑制作用。其对卵巢癌生长的抑制作用机制可能是通过减少新生血管形成和降低血管生成因子的表达来介导的。

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