title: [Modulation of colon cancer cell invasiveness induced by deoxycholic acid].
abstract: OBJECTIVE
  Deoxycholic acid (DCA), a secondary bile acid, has been implicated to promote colon cancer growth and progression. However, its molecular mechanisms are largely unknown. In this study, we investigated the effects of DCA on proliferation, migration, and invasiveness of colon cancer cells (HT-29).
  
  
  METHODS
  HT-29 cells were incubated with either medium (control) only or DCA for 24-48 hours. Time courses of RT-PCR for vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha mRNA expression, Western blotting for VEGF and matrix metalloproteinase (MMP)-9, zymography for MMP-9 activation, and wound-migration assay were determined after various concentrations of DCA (0-80 microM) treatment. Moreover, these experiments were reassessed after pretreatments (2-6 hours) with specific inhibitors of various signal pathways.
  
  
  RESULTS
  DCA enhanced HIF-1alpha mRNA expression, VEGF mRNA and VEGF protein expression, MMP-9 protein expression/activation, and cell migration ability in a dose-related manner. DCA-induced VEGF protein expression was inhibited by pretreatment with NS-398 (COX-2 inhibitor), PDTC (NF-kappaB inhibitor), or tauroursodeoxycholic acid (TUDC). DCA-induced cell migration ability was inhibited by pretreatment of GF109203X, a protein kinase C inhibitor. DCA-induced MMP-9 protein expression/activation was inhibited by pretreatment with SB203580, U0126, or PDTC.
  
  
  CONCLUSIONS
  DCA significantly upregulates invasive and angiogenic potentials of human colon cancer cells through multiple signal transduction pathways.
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. hyskim@yonsei.ac.kr
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Yong Kyu
authors.initials: YK
authors.lastname: Lee
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
authors.forename: Hwa In
authors.initials: HI
authors.lastname: Jang
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003840:Deoxycholic Acid / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D003840:Deoxycholic Acid; D020780:Matrix Metalloproteinase 9