Grape Seed Proanthocyanidins Inhibit the Growth of Human Non-Small Cell Lung Cancer Xenografts by Targeting Insulin-Like Growth Factor Binding Protein-3, Tumor Cell Proliferation, and Angiogenic Factors (Publication with Expression of Concern. See vol. 24, pg. 6101, 2018)
Grape Seed Proanthocyanidins Inhibit the Growth of Human Non-Small Cell Lung Cancer Xenografts by Targeting Insulin-Like Growth Factor Binding Protein-3, Tumor Cell Proliferation, and Angiogenic Factors (Publication with Expression of Concern. See vol. 24, pg. 6101, 2018)
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DOI：
10.1158/1078-0432.ccr-08-1901
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发表时间：
2009-02-01
影响因子：
11.5
通讯作者：
Katiyar, Santosh K.
中科院分区：
文献类型：
--
作者：
Akhtar, Suhail;Meeran, Syed M.;Katiyar, Santosh K.
目的：肺癌是全球癌症相关死亡的主要原因。在这里，我们评估了葡萄籽原花青素（GSPs）对人非小细胞肺癌（NSCLC）细胞在体外和体内使用肿瘤异种移植模型的化疗效果。实验设计：GSPs对人NSCLC细胞系在细胞增殖方面的影响进行了测定。用免疫组化检测、ELISA和Western blotting.Results：在体外用GSPs处理NSCLC细胞导致细胞增殖的抑制。作为AIN 76 A对照饮食的补充，给予GSP（0.1%、0.2%和0.5%，w/w）导致无胸腺裸鼠中NSCLC（A549和H1299）肿瘤异种移植物生长的剂量依赖性抑制（25-76%; P < 0.05-0.001）。GSPs对NSCLC异种移植瘤的生长抑制作用与肿瘤微环境和血浆中胰岛素样生长因子结合蛋白-3水平的增强以及抗增殖、抗血管生成和促凋亡作用有关。结论：本临床前研究首次揭示了饮食GSPs具有抑制无胸腺裸鼠体内生长的人NSCLC肿瘤异种移植瘤生长的能力。需要更多的研究来开发GSPs作为预防人类肺癌的药物。
Purpose: Lung cancer is a leading cause of cancer-related deaths worldwide. Here, we assessed the chemotherapeutic effect of grape seed proanthocyanidins (GSPs) on human non-small Cell lung cancer (NSCLC) cells in vitro and in vivo using a tumor xenograft model.Experimental Design: The effects of GSPs on human NSCLC cell lines in terms of cellular proliferation were determined. The chemotherapeutic effects of a GSP-supplemented AIN76A control diet fed to nude mice bearing tumor xenografts (A549 and H1299) were evaluated in terms of biomarkers of cell proliferation and angiogenesis and on insulin-like growth factor binding protein-3 using immunohistochemical detection, ELISA, and Western blotting.Results: In vitro treatment of NSCLC cells with GSPs resulted in inhibition of cellular proliferation. Administration of GSPs (0.1%, 0.2%, and 0.5%, w/w) as a supplement of an AIN76A control diet resulted in a dose-dependent inhibition of the growth of NSCLC (A549 and H1299) tumor xenografts in athymic nude mice (25-76%; P < 0.05-0.001). The growth-inhibitory effect of GSPs on the NSCLC xenograft tumors was associated with the enhancement of the levels of insulin-like growth factor binding protein-3 in the tumor microenvironment and plasma and antiproliferative, antiangiogenic, and proapoptotic effects.Conclusions: This preclinical Study reveals for the first time that dietary GSPs have the ability to inhibit the growth of human NSCLC tumor xenografts grown in vivo in athymic nude mice. More studies are needed to develop GSPs as a pharmacologically safe agent for the prevention of lung cancer in humans.