Zhao Kai, Yuan Yang, Lin Binyan, Miao Zhaorui, Li Zhiyu, Guo Qinglong, Lu Na
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
Gene. 2018 Feb 5;642:533-541. doi: 10.1016/j.gene.2017.11.065. Epub 2017 Dec 12.
LW-215 is a newly synthesized flavonoid, which is the derivative of wogonin. Our group has previously confirmed that wogonin has an anti-angiogenic activity, while the anti-angiogenic effect of LW-215 is unclear. In this study, we explored whether LW-215 can inhibit angiogenesis and further probed the potential molecular mechanisms. We found that LW-215 inhibited migration and tube formation in human umbilical vein endothelial cells (HUVECs) and immortalized endothelial EA.hy926 cells without a significant decrease in cell viability. Microvessels sprouting from rat aortic ring and chicken chorioallantoic membrane (CAM) model also revealed that LW-215 could suppress angiogenesis in vivo. Western blot and ELISA analysis indicated that LW-215 could prevent VEGFR2 activation though reducing VEGF autocrine other than VEGFR1. Thus, its downstream kinases, such as Akt, ERK and p38 signaling, were inhibited. Taken together, these results fully showed that LW-215 might be a promising anti-angiogenesis agent.
LW-215是一种新合成的黄酮类化合物，是汉黄芩素的衍生物。我们团队之前已经证实汉黄芩素具有抗血管生成活性，而LW-215的抗血管生成作用尚不清楚。在本研究中，我们探讨了LW-215是否能抑制血管生成，并进一步探究其潜在的分子机制。我们发现LW-215抑制人脐静脉内皮细胞（HUVECs）和永生化内皮EA.hy926细胞的迁移和管腔形成，而细胞活力没有显著下降。从大鼠主动脉环和鸡胚绒毛尿囊膜（CAM）模型中长出的微血管也表明LW-215可以在体内抑制血管生成。蛋白质免疫印迹和酶联免疫吸附测定分析表明，LW-215可通过减少VEGF自分泌而非VEGFR1来阻止VEGFR2激活。因此，其下游激酶，如Akt、ERK和p38信号通路被抑制。综上所述，这些结果充分表明LW-215可能是一种有前景的抗血管生成药物。
