Korean J Gastroenterol.  2006 Jul;48(1):9-18.

Modulation of Colon Cancer Cell Invasiveness Induced by Deoxycholic Acid

• Kim HS
• Lee YK
• Kim JW
• Baik SK
• Kwon SO
• Jang HI

Abstract

BACKGROUND/AIMS
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 (0-80mum) 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.

Keyword

Deoxycholic acid; HT-29 colon cancer cells; Invasiveness; Angiogenesis

MeSH Terms

Cell Movement/drug effects
Colonic Neoplasms/metabolism/pathology/*physiopathology
Deoxycholic Acid/*pharmacology
HT29 Cells
Humans
Hypoxia-Inducible Factor 1/metabolism
Matrix Metalloproteinase 9/metabolism
Neoplasm Invasiveness
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction/drug effects
Vascular Endothelial Growth Factor A/metabolism