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.%目的 探讨过氧化物酶体增殖激活受体-γ(PPAR-γ)高亲和力配体-噻唑烷二酮类药物曲格列酮对大鼠垂体腺瘤GH3细胞系增殖的影响.并初步探讨其作用机制. 方法 不同浓度的曲格列酮作用于GH3细胞,用MTT法检测各组GH3细胞生长情况,用流式细胞技术检测各组GH3细胞周期的变化,用半定量RT-PCR方法 检测各组GH3细胞CyclinD1基因mRNA的表达.结果 曲格列酮干预GH3细胞72 h后.以浓度效应关系抑制GH3细胞增殖,并使GH3细胞明显被阻滞于G1/S检测点,CyclinD1 mRNA表达明显减少,与对照组比较差异有统计学意义(P<0.05). 结论 曲格列酮能明显抑制大鼠垂体腺瘤细胞的增殖,其分子机制可能是其与PPAR-γ结合后导致CyclinD1 mRNA表达减少,从而抑制了细胞增殖,促进肿瘤细胞死亡.
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