Troglitazone inhibits rat pituitary adenoma GH3 cell growth by activating peroxisome proliferator-activated receptor-gamma to suppress cyclin DI transcription

Abstract

Objective To study the inhibitory effects of troglitazone on the proliferation of rat pituitary adenoma GH3 cell line in vitro and explore the mechanisms. Methods GH3 cells were treated with troglitazone at different concentrations (1×10-7, 1×10-6and 1×10-5 mol/L), dimethyl sulfoxide (DMSO) (DMSO control group) or phenol red- and serum-free F-12 medium (blank control group). MTT assay and flow cytometry was used to detect the cell growth and the cell cycle distribution after the treatment, respectively. Semi-quantitative RT-PCR was performed to detect the expression of cyclin D1 mRNA. Results Troglitazone treatment for 72 h significantly inhibited the cell proliferation and induced obvious G1/S cell cycle arrest and cell death. Compared to those in the blank control and DMSO-treated cells, troglitazone also significantly decreased the expression ofcyclin 1I mR_NA in the GH3 cells in a concentration-dependent manner (P<0.05). Conclusion Troglitazone can obviously inhibit the proliferation of GH3 cells possibly through the mechanism of decreasing cyclin D1 mRNA after its binding to peroxisome proliferator-activated receptor-γ, which induces G1 cell-cycle arrest and promotes cell death. Key words: Pituitary adenoma; Troglitazone; Thiazolidinedione compounds; Cell proliferation; Activating peroxisome proliferator-activated receptor-gamma