title: Dihydroartemisinin inhibits angiogenesis in pancreatic cancer by targeting the NF-κB pathway.
abstract: OBJECTIVE
  Dihydroartemisinin (DHA) has recently shown antitumor activity in human pancreatic cancer cells. However, its effect on antiangiogenic activity in pancreatic cancer is unknown, and the mechanism is unclear. This study was aimed to investigate whether DHA would inhibit angiogenesis in human pancreatic cancer.
  
  
  METHODS
  Cell viability and proliferation, tube formation of human umbilical vein endothelial cells (HUVECs), nuclear factor (NF)-κB DNA-binding activity, expressions of vascular endothelial growth factor (VEGF), interleukin (IL)-8, cyclooxygenase (COX)-2, and matrix metalloproteinase (MMP)-9 were examined in vitro. The effect of DHA on antiangiogenic activity in pancreatic cancer was also assessed using BxPC-3 xenografts subcutaneously established in BALB/c nude mice.
  
  
  RESULTS
  DHA inhibited cell proliferation and tube formation of HUVECs in a time- and dose-dependent manner and also reduced cell viability in pancreatic cancer cells. DHA significantly inhibited NF-κB DNA-binding activity, so as to tremendously decrease the expression of NF-κB-targeted proangiogenic gene products: VEGF, IL-8, COX-2, and MMP-9 in vitro. In vivo studies, DHA remarkably reduced tumor volume, decreased microvessel density, and down-regulated the expression of NF-κB-related proangiogenic gene products.
  
  
  CONCLUSIONS
  Inhibition of NF-κB activation is one of the mechanisms that DHA inhibits angiogenesis in human pancreatic cancer. We also suggest that DHA could be developed as a novel agent against pancreatic cancer.
authors.affiliation: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 23 Youzheng Str, Nangang, Harbin, People's Republic of China.
authors.forename: Shuang-Jia
authors.initials: SJ
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.forename: Zhuo-Xin
authors.initials: ZX
authors.lastname: Cheng
authors.forename: Hao-Xin
authors.initials: HX
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.forename: Rui
authors.initials: R
authors.lastname: Kong
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Hong-Chi
authors.initials: HC
authors.lastname: Jiang
authors.forename: Shang-Ha
authors.initials: SH
authors.lastname: Pan
authors.forename: Dong-Bo
authors.initials: DB
authors.lastname: Xue
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Bai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D037621:Artemisinins; D016328:NF-kappa B; C039060:artenimol