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汉黄芩素通过抑制 PI3K/Akt/NF-κB 信号通路抑制 LPS 诱导的肿瘤血管生成。

Wogonin inhibits LPS-induced tumor angiogenesis via suppressing PI3K/Akt/NF-κB signaling.

机构信息

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People׳s Republic of China.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People׳s Republic of China.

出版信息

Eur J Pharmacol. 2014 Aug 15;737:57-69. doi: 10.1016/j.ejphar.2014.05.011. Epub 2014 May 22.

Abstract

Wogonin has been shown to have anti-angiogenesis and anti-tumor effects. However, whether wogonin inhibits LPS-induced tumor angiogenesis is not well known. In this study, we investigated the effect of wogonin on inhibiting LPS-induced tumor angiogenesis and further probed the underlying mechanisms. ELISA results revealed that wogonin could suppress LPS-induced VEGF secretion from tumor cells. Transwell assay, tube formation assay, rat aortic ring assay and CAM model were used to evaluate the effect of wogonin on angiogenesis induced by MCF-7 cell (treated with LPS) in vitro and in vivo. The inhibitory effect of wogonin on angiogenesis in LPS-treated MCF-7 cells was then confirmed by the above in vitro and in vivo assays. The study of the molecular mechanism showed that wogonin could suppress PI3K/Akt signaling activation. Moreover, wogonin inhibited nuclear translocation of NF-κB and its binding to DNA. The result of real-time PCR and luciferase reporter assay suggested that VEGF expression was down-regulated by wogonin primarily at the transcriptional level. IGF-1 and p65 expression plasmid were used to activate PI3K/Akt and NF-κB pathways, and to observe the effect of wogonin on the simualtion of PI3K/Akt/NF-κB signaling. Taken together, the result suggested that wogonin was a potent inhibitor of tumor angiogenesis and provided a new insight into the mechanisms of wogonin against cancer.

摘要

汉黄芩素具有抗血管生成和抗肿瘤作用。然而,汉黄芩素是否抑制 LPS 诱导的肿瘤血管生成尚不清楚。在这项研究中,我们研究了汉黄芩素抑制 LPS 诱导的肿瘤血管生成的作用,并进一步探讨了其潜在的机制。ELISA 结果表明,汉黄芩素可以抑制 LPS 诱导的肿瘤细胞 VEGF 分泌。Transwell assay、管形成 assay、大鼠主动脉环 assay 和 CAM 模型用于评估汉黄芩素对体外和体内 MCF-7 细胞(用 LPS 处理)诱导的血管生成的影响。通过上述体外和体内实验证实了汉黄芩素对 LPS 处理的 MCF-7 细胞血管生成的抑制作用。分子机制研究表明,汉黄芩素可以抑制 PI3K/Akt 信号通路的激活。此外,汉黄芩素抑制 NF-κB 的核转位及其与 DNA 的结合。实时 PCR 和荧光素酶报告基因检测结果表明,汉黄芩素主要通过转录水平下调 VEGF 的表达。使用 IGF-1 和 p65 表达质粒激活 PI3K/Akt 和 NF-κB 通路,并观察汉黄芩素对 PI3K/Akt/NF-κB 信号模拟的影响。综上所述,结果表明汉黄芩素是一种有效的肿瘤血管生成抑制剂,为汉黄芩素抗肿瘤作用的机制提供了新的见解。

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