Inhibitory effect of prostaglandin delta 12-PGJ2 on cell proliferation and alpha-fetoprotein expression in HuH-7 human hepatoma cells

Prostaglandins. 1992 Feb;43(2):189-97. doi: 10.1016/0090-6980(92)90086-9.

Abstract

9-deoxy-delta 9,delta 12-13,14-dihydro-prostaglandin D2 (delta 12-PGJ2) is a potent inhibitor of proliferation of tumor cells. In the present study, the effect of delta 12-PGJ2 on the alpha-fetoprotein(AFP) and the albumin gene expression was analyzed in HuH-7 human hepatoma cells. delta 12-PGJ2 inhibited the cell growth and reduced the medium AFP concentrations dose-dependently. To determine whether this decline of AFP depends only on the relative decrease in cell numbers by delta 12-PGJ2, or is in part, due to the decrease in the cellular AFP synthesis by delta 12-PGJ2, Northern blot analysis was performed in this study. By Northern blotting, it was shown that delta 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the level of the beta-actin mRNA was not changed by delta 12-PGJ2. In the transient chloramphnicol acetyltransferase plasmid transfection experiments, delta 12-PGJ2 did not suppress the AFP enhancer activity, which possibly regulates both the AFP and the albumin gene expression in HuH-7 hepatoma cells, but resulted in the selective repression of the AFP and the albumin promoter activity. These results suggest that delta 12-PGJ2 suppresses not only cell growth but also expression of the AFP gene and the albumin gene at the transcriptional level in human hepatoma cells.

MeSH terms

  • Albumins / genetics
  • Blotting, Northern
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Division / drug effects*
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Promoter Regions, Genetic
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • alpha-Fetoproteins / biosynthesis
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / metabolism*

Substances

  • Albumins
  • RNA, Messenger
  • alpha-Fetoproteins
  • 9-deoxy-delta-9-prostaglandin D2
  • Chloramphenicol O-Acetyltransferase
  • Prostaglandin D2