Reactivation of IGFBP7 by DNA demethylation inhibits human colon cancer cell growth in vitro

Cancer Biol Ther. 2008 Dec;7(12):1896-900. doi: 10.4161/cbt.7.12.6937. Epub 2008 Dec 7.

Abstract

Background: The insulin-like growth factor binding protein 7 (IGFBP7) gene is regulated by DNA methylation in colon cancer, which was identified in our previous study. In this study, we examined the effects of DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) on IGFBP7 reactivation and cell biological behaviors in vitro to investigate a potential role for 5-aza-dC in treating colorectal cancer.

Results: 5-aza-dC treatment showed induction of IGFBP7 transcription in these cancer cells. It consequently led to inhibition of cell growth, cell cycle arrest and apoptosis, suppression of cell migration and invasion in colon cancer cell lines.

Methods: We examined the effects of 5-aza-dC on reexpression of previously silenced IGFBP7 and its global effects on cell cycle, apoptosis, migration and invasion in three colon cancer cell lines, SW620, HT29 and COLO205.

Conclusion: Our findings indicate that 5-aza-dC may have anticancer function for colon cancer and restoration of IGFBP7 may involve in the biological effects induced by 5-aza-dC in colon cancer cell lines. These data suggest that 5-aza-dC has clinical potential in the treatment of colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • DNA / genetics*
  • DNA Methylation
  • Decitabine
  • G1 Phase / drug effects
  • G1 Phase / genetics
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / drug effects
  • Insulin-Like Growth Factor Binding Proteins / genetics*
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • Transcription, Genetic

Substances

  • Insulin-Like Growth Factor Binding Proteins
  • RNA, Messenger
  • insulin-like growth factor binding protein-related protein 1
  • Decitabine
  • DNA
  • Azacitidine