title: Synergistic effects of β-catenin inhibitors and sorafenib in hepatoma cells.
abstract: OBJECTIVE
  The kinase inhibitor sorafenib is the only approved drug which is effective against late-stage hepatocellular carcinoma (HCC). However, the mean survival of patients is still less than one year, making new approaches for tumor treatment essential. Oncogenic signaling through β-catenin is frequently overactivated in HCC and therefore a potential target for a combination therapy with sorafenib.
  
  
  METHODS
  Two hepatoma cell lines were treated with non-cytotoxic concentrations of sorafenib and different β-catenin inhibitors. The tumor-relevant end-points of proliferation, apoptosis, cell migration, and colony formation were assessed in vitro along with the activity of the Wingless/Int-1(WNT)/β-catenin and mitogen-activated protein kinase pathways.
  
  
  RESULTS
  Combined treatment with sorafenib and β-catenin inhibitors synergized in the inhibition of cell proliferation, migration, colony formation ability, and induction of apoptosis.
  
  
  CONCLUSIONS
  In vitro data suggest that the combination of sorafenib and β-catenin inhibition might be a promising approach for HCC treatment.
authors.affiliation: Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Muche
authors.affiliation: Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
authors.forename: Melissa
authors.initials: M
authors.lastname: Kirschnick
authors.affiliation: Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany albert.braeuning@uni-tuebingen.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Braeuning
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D051176:beta Catenin; D009536:Niacinamide; D000077157:Sorafenib
keywords: Hepatocellular carcinoma; MAPK signaling; Wnt signaling; liver tumor