title: Inhibitory CpG sequences reduced ischemia/reperfusion-induced hepatic metastases of liver tumor in a murine model.
abstract: BACKGROUND
  It is reported that hepatic ischemia/reperfusion (I/R) during hepatectomy accelerates liver tumor growth. Hepatic I/R induces inflammation cytokines, which can accelerate the outgrowth of liver tumor. Inhibitory CpG sequence (iCpG) is an inhibitor of TLR9, which plays an important role in hepatic I/R. The aim of this study was to examine whether iCpG could prevent hepatic I/R-induced metastases of the liver tumor.
  
  
  METHODS
  A murine tumor model that underwent partial hepatic I/R or sham operation was treated with iCpG or control DNA sequence (Ctrl ODN). Tumor growth and metastases were observed on day 14 after surgery; Endothelial leukocyte adhesion molecules such as E-selectin and intracellular adhesion molecule-1 (ICAM-1) protein expression were measured 24 h after reperfusion by Western blotting; E-selectin and ICAM-1 mRNA expression in hepatic tissue was measured 2 h after reperfusion by RT-PCR; NF-κB activity in hepatic tissue was measured 2 h after reperfusion by electrophoretic gel mobility shift assay.
  
  
  RESULTS
  The tumor growth in the mice subjected to hepatic I/R was remarkably stimulated when compared with the mice subjected to laparotomy alone. The iCpG had no significant inhibitory effect on tumor growth in sham-operated mice subjected to tumor. However, iCpG could reduce the tumor growth and inhibit the activation of NF-κB and downregulate the E-selectin and ICAM-1 mRNA and protein in the mice with tumor subjected to I/R.
  
  
  CONCLUSIONS
  ICpG might reduce I/R-induced hepatic metastases of liver tumor cells by inhibiting NF-κB expression and downregulating the adhesive molecules, such as E-selectin and ICAM-1.
authors.affiliation: Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Aiqun
authors.initials: A
authors.lastname: Zhang
authors.forename: Chonghui
authors.initials: C
authors.lastname: Li
authors.forename: Jiahong
authors.initials: J
authors.lastname: Dong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D006498:Hepatectomy; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007813:Laparotomy; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015226:Dinucleoside Phosphates; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1; D016328:NF-kappa B; D012333:RNA, Messenger; D051217:Toll-Like Receptor 9; C495370:Tlr9 protein, mouse; C015772:CpG dinucleotide