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Oridonin exhibits anti-angiogenic activity in human umbilical vein endothelial cells by inhibiting VEGF-induced VEGFR-2 signaling pathway
Institution:1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China;2. West China School of Public health, Sichuan University, Chengdu, China;3. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China;4. Guangdong Provincial Stomatological Hospital & the Affiliated Stomatological Hospital of Southern Medical University, Guangzhou, China;1. Rungta College of Pharmaceutical Sciences and Research, Bhilai, India;2. Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India;3. Shri Shankara Technical Campus, Shri Shankara Group of Institutions, Faculty of Pharmaceutical Sciences, Bhilai, India
Abstract:Oridonin has been found to be a potential anti-angiogenesis agent. However, its functional targets and the underlying mechanisms are still vague. In vitro studies we found that oridonin not only inhibited VEGF-induced cell proliferation, migration and tube formation but also caused G2/M phase arrest and triggered cellular apoptosis in HUVECs. In mechanistic studies revealed that oridonin exhibited the anti-angiogenic potency, at least in part, through the down-regulation of VEGFR2-mediated FAK/MMPs, mTOR/PI3K/Akt and ERK/p38 signaling pathways which led to reduced invasion, migration, and tube formation in HUVECs. Our results could provide evidence that oridonin exerts strong anti-angiogenesis activities via specifically targeting VEGFR2 and its signaling pathway.
Keywords:Oridonin  Anti-angiogenesis  VEGF  VEGFR2  HUVECs
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