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

Abstract

9-deoxy-Δ 9, Δ 12-13,14-dihydro-prostaglandin D2 (Δ 12-PGJ2) is a potent inhibitor of proliferation of tumor cells. In the present study, the effect of Δ 12-PGJ2 on the α-fetoprotein (AFP) and the albumin gene expression was analyzed in HuH-7 human hepatoma cells. Δ 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 Δ 12-PGJ2, or is in part, due to the decrease in the cellular AFP synthesis by Δ 12-PGJ2, Northern blot analysis was performed in this study. By Northern blotting, it was shown that Δ 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the level of the β-actin mRNA was not changed by Δ 12-PGJ2. In the transient chloramphnicol acetyltransferase plasmid transfection experiments, Δ 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 Δ 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.