title: Cryptotanshinone inhibits VEGF-induced angiogenesis by targeting the VEGFR2 signaling pathway.
abstract: Anti-angiogenesis has been proposed as an important strategy for angiogenesis-related diseases. Cryptotanshinone (CPT), an active component of Salvia miltiorrhiza, may be a potential inhibitor of angiogenesis. However, the molecular mechanisms underlying its anti-angiogenic activities remain poorly understood. This study is to investigate the effects of CPT on VEGF-induced angiogenesis and VEGFR2 signaling pathway in human umbilical vein endothelial cells (HUVECs).
  
  
  
  HUVECs were treated with different concentration of CPT (5-20μmol/L) and the viability, endothelial cell migration, invasion, and tubular-like structure formation of HUVECs were detected by MTT, wound-healing migration, Transwell invasion and Matrigel tube formation assays, respectively. To assess the effect of CPT on VEGFR2 signaling pathway, VEGF-induced phosphorylation of VEGFR2 and its downstream molecules, including ERK1/2, p90RSK, Src and FAK were analyzed by Western blot.
  
  
  
  CPT significantly suppressed VEGF-induced cells proliferation, migration, invasion, and tubular-like structure formation in HUVECs in a dose- and time-dependent manner. Western blot results revealed that CPT significantly suppressed VEGF-induced phosphorylation of VEGFR2 and its key downstream protein kinases, including p-ERK1/2, p-p90RSK, pY416-Src and pY576/577-FAK, which are responsible for endothelial cell migration, proliferation, and survival.
  
  
  
  Our study suggested that CPT potently inhibits VEGF-induced angiogenesis by suppressing VEGFR2 activation and its downstream Src/FAK and ERK1/2 signaling pathways in HUVECs, highlighting the therapeutic potential for the treatment of angiogenesis-related diseases.
authors.affiliation: Department of Cardiology, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.affiliation: ShanXi Cardiovascular Hospital, Taiyuan, ShanXi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Xinbin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Nanyang
authors.initials: N
authors.lastname: Zhou
authors.affiliation: First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Department of Cardiology, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Cardiology, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China. Electronic address: ajiedoctor@163.com.
authors.forename: Shenjie
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, Zhejiang, China. Electronic address: maoweilw@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Mao
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D010616:Phenanthrenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C037886:cryptotanshinone; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Angiogenesis; Cryptotanshinone; Human umbilical vein endothelial cell; VEGFR2 signaling pathway