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血管活性肠肽在异种移植模型中增强人实验性前列腺癌的生长和血管生成。

Vasoactive intestinal peptide enhances growth and angiogenesis of human experimental prostate cancer in a xenograft model.

作者信息

Collado Beatriz, Carmena María J, Clemente Celia, Prieto Juan C, Bajo Ana M

机构信息

Department of Biochemistry and Molecular Biology, University of Alcalá, Alcalá de Henares 28871, Spain.

出版信息

Peptides. 2007 Sep;28(9):1896-901. doi: 10.1016/j.peptides.2007.04.015. Epub 2007 May 3.

Abstract

We show that vasoactive intestinal peptide (VIP) exerts trophic and proangiogenic activities in experimental prostate cancer in vivo. Nude mice were subcutaneously injected with Matrigel impregnated with LNCaP prostate cancer cells. Cell treatment with 100 nM VIP for 1h before xenograft resulted in increased tumor growth after 8 and, more remarkably, 15 days of injection. The same occurred with the mRNA expression of the main angiogenic factor, vascular endothelial growth factor (VEGF), as shown by real-time RT-PCR quantification. The proangiogenic activity of VIP was further established by showing increases of hemoglobin levels, Masson trichromic staining, and immunohistochemical CD34 staining in tumors excised 15 days after subcutaneous injection of VIP-treated cells as compared to control conditions. All these parameters indicate that VIP increases vessel formation. This xenograft model is a useful tool to study in vivo the effects of VIP-related peptides in tumor growth and development of blood supply as well as their therapeutical potential in prostate cancer.

摘要

我们发现,血管活性肠肽(VIP)在体内实验性前列腺癌中发挥营养和促血管生成活性。将裸鼠皮下注射接种了LNCaP前列腺癌细胞的基质胶。在异种移植前用100 nM VIP处理细胞1小时,导致注射8天及更显著地在15天后肿瘤生长增加。实时逆转录聚合酶链反应(RT-PCR)定量显示,主要血管生成因子血管内皮生长因子(VEGF)的mRNA表达也出现同样情况。与对照条件相比,皮下注射VIP处理细胞15天后切除的肿瘤中血红蛋白水平升高、Masson三色染色和免疫组化CD34染色增加,进一步证实了VIP的促血管生成活性。所有这些参数表明VIP增加血管形成。这种异种移植模型是一种有用的工具,可用于在体内研究VIP相关肽对肿瘤生长和血供发育的影响及其在前列腺癌中的治疗潜力。

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