title: Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin.
abstract: BACKGROUND
  Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects.
  
  
  METHODS
  Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects.
  
  
  RESULTS
  Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs.
  
  
  CONCLUSIONS
  These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis.
authors.forename: Chen-Chieh
authors.initials: CC
authors.lastname: Yang
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Chang
authors.forename: Jian-Kang
authors.initials: JK
authors.lastname: Chao
authors.forename: Yi-Liang
authors.initials: YL
authors.lastname: Lai
authors.forename: Wei-En
authors.initials: WE
authors.lastname: Chang
authors.forename: Wen-Hsiu
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Armed-Forces Hualien General Hospital, Hualien 97144, Taiwan. wuhsienku@gmail.com.
authors.forename: Wu-Hsien
authors.initials: WH
authors.lastname: Kuo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D052243:Resistin / Q000502:physiology*
chemical_list: D052243:Resistin; D055372:AMP-Activated Protein Kinases