title: Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis.
abstract: BACKGROUND
  Emodin has been showed to induce apoptosis of pancreatic cancer cells and inhibit tumor growth in our previous studies. This study was designed to investigate whether emodin could inhibit the angiogenesis of pancreatic cancer tissues and its mechanism.
  
  
  RESULTS
  In accordance with our previous study, emodin inhibited pancreatic cancer cell growth, induced apoptosis, and enhanced the anti-tumor effect of gemcitabine on pancreatic caner cells in vitro and in vivo by inhibiting the activity of NF-κB. Here, for the first time, we demonstrated that emodin inhibited tumor angiogenesis in vitro and in implanted pancreatic cancer tissues, decreased the expression of angiogenesis-associated factors (NF-κB and its regulated factors VEGF, MMP-2, MMP-9, and eNOS), and reduced eNOS phosphorylation, as evidenced by both immunohistochemistry and western blot analysis of implanted tumors. In addition, we found that emodin had no effect on VEGFR expression in vivo.
  
  
  CONCLUSIONS
  Our results suggested that emodin has potential anti-tumor effect on pancreatic cancer via its dual role in the promotion of apoptosis and suppression of angiogenesis, probably through regulating the expression of NF-κB and NF-κB-regulated angiogenesis-associated factors.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. wzf2lsz@163.com
authors.forename: Sheng-Zhang
authors.initials: SZ
authors.lastname: Lin
authors.forename: Wei-Tian
authors.initials: WT
authors.lastname: Wei
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Kang-Jie
authors.initials: KJ
authors.lastname: Chen
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Tong
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Ni
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Liu
authors.forename: Hong-Chun
authors.initials: HC
authors.lastname: Guo
authors.forename: Dian-Lei
authors.initials: DL
authors.lastname: Liu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004642:Emodin / Q000494:pharmacology / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D047368:Tumor Burden / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016328:NF-kappa B; D042442:Vascular Endothelial Growth Factors; D052250:Nitric Oxide Synthase Type III; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004642:Emodin