Effect of dexamethasone and transforming growth factor β1, on expression of plasminogen activator inhibitor-1 in human ovarian cancer cell line HO-8910

Objective: To observe the effect of dexamethasone (Dex) and transforming growth factor β1 (TGFβ1,) on the expression of plasminogen activator inhibitor-1 (PAI-1) in human ovarian cancer cell line HO-8910, and to explore its role in the development and progression of human ovarian cancer. Methods: Human HO-8910 cells were treated with Dex(100 nmol/L) or TGFβ1, (0.01-10 ng/ml) or both for different time periods, then the expression of PAI-1 mRNA and protein was examined by real-time PCR and Western blotting analysis. Act D was used to inhibit the synthesis of new mRNA so as to evaluate the stability of PAI-1 mRNA. Results: TGFβ1, up-regulated PAI-1 mRNA expression in HO-8910 cells in a time- and dose-dependent manner, with the highest increase being 3.75 folds (P<0.01); Dex also up-regulated PAI-I mRNA expression, with the highest increase being 1.65 folds (P<0.01). Dex combined with TGFβ1 markedly up-regulated PAI-1 mRNA level, with the highest increase being 12.7 folds (P<0.01), which was greatly higher than the sum of Dex and TGFβ1. Dex combined with TGFβ1 also greatly up-regulated the PAI-1 protein level compared with Dex or TGFβ1 alone. Dex, TGFβ1 or combination of them did not affect the stability of PAI-1 mRNA. Conclusion: Both Dex and TGFβ1 can up-regulate the expression of PAI-1 in HO-8910 cells, and the combination of them can work synergistically to up-regulate PAI-1 expression. The synergistic effect occurs at the transcriptional level, and it is not due to enhenced stability of PAI-1 mRNA.