title: Paris Saponin II suppresses the growth of human ovarian cancer xenografts via modulating VEGF-mediated angiogenesis and tumor cell migration.
abstract: OBJECTIVE
  Paris Saponin II (PSII) is an active component of Rhizoma Paridis-an essential ingredient in traditional Chinese herbal medicines. PSII can induce cytotoxic effects in cancer cells and inhibit ovarian cancer growth. Since pathological angiogenesis (henceforth, angiogenesis) is often associated with gynecological cancers, here, we investigated whether PSII renders effects on angiogenesis and examined possible molecular mechanisms underlying the effects of PSII.
  
  
  METHODS
  The effects of PSII on the biofunctions of endothelial cells (EC), the crucial components of blood vessels, were examined by standardized angiogenesis in vitro and ex vivo assays, Western blot analysis, ELISA, and kinase assay. Angiogenesis in a xenograft mouse model of ovarian cancer was evaluated by color Doppler ultrasound and immunohistochemistry.
  
  
  RESULTS
  PSII exerted marked inhibitory effect on the growth of VEGF-stimulated human umbilical vein endothelial cells in a dose-time-dependent manner, inhibited cell's motility, and interfered with tubulogenesis. PSII also blocked microvessel outgrowth in a rat aortic ring assay and compromised angiogenesis in a mouse model of ovarian carcinoma using either SKOV3 or HOC-7 cell lines. VEGF levels in PSII-treated EC and tumor cells were reduced. In EC, PSII blocked the activation of VEGFR2 in dose-dependent manner leading to the reduction of VEGF-induced phosphorylation on several intracellular pro-angiogenic kinase, including the extracellular signal-related kinase, Src family kinase, focal adhesion kinase, and AKT kinase.
  
  
  CONCLUSIONS
  The results provided the first insight into the anti-angiogenesis properties of Saponin family in solid tumors and suggested a promising therapeutic potential of PSII in the ovarian cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xiao
authors.forename: Juan
authors.initials: J
authors.lastname: Zou
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Shanling
authors.initials: S
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Bai
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004144:Diosgenin / Q000031:analogs & derivatives; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D042461:Vascular Endothelial Growth Factor A; C067584:formosanin C; D004144:Diosgenin