title: Triptolide augments the effects of 5-lipoxygenase RNA interference in suppressing pancreatic tumor growth in a xenograft mouse model.
abstract: OBJECTIVE
  Pancreatic cancer has one of the highest fatality rates of all cancers, and new strategies or reagents to tackle this disease are needed. Triptolide (TL) is able to potently inhibit the growth of pancreatic tumor cells in vitro. On the other hand, blockage of 5-LOX pathway might be useful for treatment of pancreatic cancer. In the current study, we tested the effects of 5-LOX RNA interference and TL individually or in combination in suppressing human pancreatic tumor growth in xenograft mouse model.
  
  
  METHODS
  5-LOX short hairpin RNA (shRNA) vectors were developed and screened out for their efficacy in human pancreatic cancer cell line SW1990 in vitro. Their antitumor effects were also evaluated by measuring cell proliferation and apoptosis. An effective 5-LOX shRNA was given alone or in combination with TL to treat pancreatic tumor xenograft. Expression levels of 5-LOX and VEGF were measured with Western blotting and immunohistology.
  
  
  RESULTS
  Knocking down 5-LOX gene suppressed cancer cell growth in vitro and intra-tumoral delivering of 5-LOX shRNA inhibited growth of transplanted tumor in vivo. TL treatment induced tumor suppression and greatly enhanced antitumor effects of 5-LOX shRNA in the mouse model. 5-LOX RNA interference or TL treatment suppresses VEGF expression in tumor tissue, and combined treatment further reduces its expression.
  
  
  CONCLUSIONS
  Both treatments exerted antitumor effects in vivo, and combined use of the two approaches produced more powerful antitumor effects. Synergistic effects of combined treatment in VEGF expression may contribute to the mechanisms of the strong antitumor effects.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001 Nangtong, Jiangsu, People's Republic of China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ding
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Jingdan
authors.initials: J
authors.lastname: Qing
authors.forename: Hui
authors.initials: H
authors.lastname: Qiang
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D034741:RNA, Small Interfering; D042442:Vascular Endothelial Growth Factors; C001899:triptolide; D001094:Arachidonate 5-Lipoxygenase