Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the Notch signaling.
Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the Notch signaling.
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冬凌草甲素通过阻断 Notch 信号传导来抗血管生成，从而抑制肿瘤生长和转移
DOI：
10.1371/journal.pone.0113830
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yi Z
中科院分区：
文献类型：
--
作者：
Dong Y;Zhang T;Li J;Deng H;Song Y;Zhai D;Peng Y;Lu X;Liu M;Zhao Y;Yi Z
虽然在了解天然二萜类化合物组分冬凌草甲素对肿瘤细胞的抗炎和抗增殖作用方面取得了重大进展，但对其对肿瘤血管生成或转移的作用以及潜在的分子机制知之甚少。在这项研究中，冬凌草甲素显着抑制人脐静脉内皮细胞（HUVECs）的增殖，迁移，和毛细血管样结构的形成在体外。采用主动脉环实验和小鼠角膜血管生成模型，我们发现冬凌草甲素在体外和体内均能抑制血管生成。在我们的动物实验中，冬凌草甲素抑制肿瘤的生长和转移。免疫组化结果显示，冬凌草甲素能显著降低移植瘤组织中CD 31和vWF蛋白的表达。此外，冬凌草甲素增强内皮细胞-细胞连接，并削弱乳腺癌细胞的跨内皮迁移。从机制上讲，冬凌草甲素不仅下调了Jagged 2的表达和Notch 1的活性，而且还降低了其靶基因的表达。综上所述，我们的研究结果证明了冬凌草甲素在抑制肿瘤血管生成中的原始作用，并提出了一种机制。本研究也为Notch在肿瘤血管生成中的中心作用提供了新的证据，并表明冬凌草甲素可能是血管生成相关疾病的潜在候选药物。
While significant progress has been made in understanding the anti-inflammatory and anti-proliferative effects of the natural diterpenoid component Oridonin on tumor cells, little is known about its effect on tumor angiogenesis or metastasis and on the underlying molecular mechanisms. In this study, Oridonin significantly suppressed human umbilical vascular endothelial cells (HUVECs) proliferation, migration, and apillary-like structure formation in vitro. Using aortic ring assay and mouse corneal angiogenesis model, we found that Oridonin inhibited angiogenesis ex vivo and in vivo. In our animal experiments, Oridonin impeded tumor growth and metastasis. Immunohistochemistry analysis further revealed that the expression of CD31 and vWF protein in xenografts was remarkably decreased by the Oridonin. Furthermore, Oridonin reinforced endothelial cell-cell junction and impaired breast cancer cell transendothelial migration. Mechanistically, Oridonin not only down-regulated Jagged2 expression and Notch1 activity but also decreased the expression of their target genes. In conclusion, our results demonstrated an original role of Oridonin in inhibiting tumor angiogenesis and propose a mechanism. This study also provides new evidence supporting the central role of Notch in tumor angiogenesis and suggests that Oridonin could be a potential drug candidate for angiogenesis related diseases.
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DOI：
10.1083/jcb.200802069
发表时间：
2008-07-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nakao S;Platek A;Hirano S;Takeichi M
通讯作者：
Takeichi M
影响因子：
11.2
作者：
Shankar, Jay;Messenberg, Anat;Nabi, Ivan R.
通讯作者：
Nabi, Ivan R.
影响因子：
20.3
作者：
Longo, N;Yáñez-Mó, M;Sánchez-Mateos, P
通讯作者：
Sánchez-Mateos, P
影响因子：
2.5
作者：
Shi, Wen;Harris, Adrian L.
通讯作者：
Harris, Adrian L.
影响因子：
5.1
作者：
Kang, Ning;Zhang, Jing-Hai;Ikejima, Takashi
通讯作者：
Ikejima, Takashi