Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells

J Exp Clin Cancer Res. 2009 May 29;28(1):71. doi: 10.1186/1756-9966-28-71.

Abstract

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy with high rate of metastasis and poor prognosis. There are no effective managements to block metastasis of HCC. Programmed cell death 4 (PDCD4) is found to be a tumor transformation suppressor. Among investigations on effects of PDCD4, little is about the metastatic potentials of HCC cells. This study was to investigate the role of PDCD4 on metastatic potential of human HCC cells.

Methods: We examined the expression of PDCD4 in three HCC cell lines with different metastatic potentials, MHCC-97H (high metastatic potential), MHCC-97L (low metastatic potential) and Hep3B (no metastatic potential). A plasmid encoding PDCD4 gene was constructed and then transfected into HCC cells with the lowest PDCD4 expression level. Effects of PDCD4 on cell proliferation, cell apoptosis, gene expression of metastasis tumor antigen 1 (MTA1) and in vitro migration and invasion capacity were assessed after transfection.

Results: Our results showed that the expression level of PDCD4 was inversely correlated to the metastatic potential of HCC cells. After transfection with the PDCD4 gene, HCC cell proliferation rate was significantly decreased, cell apoptosis rate was significantly increased, the expression of MTA1 gene, HCC cell migration and Matrigel invasion were also remarkably inhibited.

Conclusion: PDCD4 expression is inversely correlated to the metastatic potential of HCC cells. PDCD4 can effectively suppress the metastatic potential of HCC cells.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / physiology*
  • Apoptosis*
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Adhesion
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Flow Cytometry
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary
  • Mice
  • NIH 3T3 Cells
  • RNA-Binding Proteins / physiology*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Trans-Activators
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Apoptosis Regulatory Proteins
  • MTA1 protein, human
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • Repressor Proteins
  • Trans-Activators
  • Histone Deacetylases