title: Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression.
abstract: BACKGROUND
  Propofol is one of the extensively and commonly used intravenous anesthetics and has the ability to influence the proliferation, motility, and invasiveness of many cancer cells. In this study, the effects of propofol on hepatocellular carcinoma cells invasion ability were examined.
  
  
  METHODS
  We assessed the invasion ability of HepG2 cells in vitro by determining enzyme activity and protein expression of MMP-9 using gelatin zymography assay and Western blot. The real-time PCR was used to evaluate the effect of propofol on microRNA-199a (miR-199a) expression, and miR-199a-2 precursor to evaluate whether over-expression of miR-199a can affect MMP-9 expression. Finally, the effect of miR-199a on propofol-induced anti-tumor activity using anti-miR-199a was assessed.
  
  
  RESULTS
  Propofol significantly elevated the expression of miR-199a and inhibited the invasiveness of HepG2 cells. Propofol also efficiently decreased enzyme activity and protein expression of MMP-9. Moreover, the over-expression of miR-199a decreased MMP-9 protein level. Interestingly, the neutralization of miR-199a by anti-miR-199a antibody reversed the effect of propofol on alleviation of tumor invasiveness and inhibition of MMP-9 activity in HepG2 cells.
  
  
  CONCLUSIONS
  Propofol decreases hepatocellular carcinoma cell invasiveness, which is partly due to the down-regulation of MMP-9 expression by miR-199a.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Wu
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Feng
authors.forename: Sheng-Mei
authors.initials: SM
authors.lastname: Zhu
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D015742:Propofol / Q000494:pharmacology*; D014162:Transfection; D015854:Up-Regulation
chemical_list: D018686:Anesthetics, Intravenous; D035683:MicroRNAs; C531408:mirn199 microRNA, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D015742:Propofol