Catechol-O-methyltransferase inhibits colorectal cancer cell proliferation and invasion

Arch Med Res. 2015 Jan;46(1):17-23. doi: 10.1016/j.arcmed.2014.12.004. Epub 2014 Dec 19.

Abstract

Background and aims: Catechol-O-methyltransferase (COMT) has been reported as an important molecule in various types of cancers. The biological function of COMT in colorectal cancer (CRC) has not yet been fully investigated.

Methods: We constructed a transient transfection of a CRC cell lines to up- and downregulate COMT expression level and tested the proliferative, invasion ability in vitro. We also constructed a stable transduced CRC cell line and conducted tumor-forming capacity experiment in mouse xenograft model in vivo.

Results: In vitro experiment showed that COMT inhibited the cell proliferation by regulating p-Akt, PTEN and inhibited G1 to S phase transition by regulating p53, p27, and cyclinD1. COMT inhibited invasion by regulating E-cadherin. In vivo experiment showed decreased tumor growth in COMT overexpressing cell line.

Conclusions: COMT has tumor-suppressive functions for CRC cell lines in vitro and in vivo experiments.

Keywords: COMT; Catechol-O-Methyltransferase; Colorectal cancer; Xenograft model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Catechol O-Methyltransferase / biosynthesis
  • Catechol O-Methyltransferase / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / genetics*
  • PTEN Phosphohydrolase / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Transfection
  • Tumor Suppressor Protein p53 / genetics

Substances

  • CCND1 protein, human
  • Cadherins
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Catechol O-Methyltransferase
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human