Matrine reduces the proliferation and invasion of colorectal cancer cells via reducing the activity of p38 signaling pathway

Acta Biochim Biophys Sin (Shanghai). 2014 Dec;46(12):1049-55. doi: 10.1093/abbs/gmu101. Epub 2014 Oct 27.

Abstract

Matrine has been used in anti-inflammatory and anti-cancer therapies for a long time. However, the anti-metastatic effect and related mechanism(s) in colorectal cancer (CRC) are still unclear. In this study, we investigated whether the administration of matrine could inhibit the proliferation, motility, and invasion of human CRC cells via regulating p38 signaling pathway. Results showed that matrine inhibited migration and invasion of CRC cells in vitro and in vivo. Additionally, after being treated with matrine for 24 h, the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 as well as proteinase activity in CRC cells were reduced in a dose-dependent manner. Moreover, matrine reduced the phosphorylation level of p38 obviously. Combined treatment with p38 inhibitor (SB203580) and matrine resulted in a synergistic reduction of invasion as well as MMP-2/-9 expression in CRC cells. It was also found that matrine inhibited the proliferation and metastasis of CRC tumor in vivo. In conclusion, p38 signaling pathway may involve in matrine's inhibitory effects on migration and invasion of CRC cells by reducing the expression of MMP-2/-9, suggesting that matrine may be a potential therapeutic agent for CRC.

Keywords: colorectal cancer; invasion; matrine; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / pathology*
  • Humans
  • Matrines
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / prevention & control*
  • Quinolizines / pharmacology*
  • Signal Transduction / drug effects*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Alkaloids
  • Quinolizines
  • p38 Mitogen-Activated Protein Kinases
  • Matrines