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曲格列酮体外抑制大鼠垂体腺瘤GH3细胞增殖
陈富勇,王守森*,王水良,王如密
0
(福建医科大学福总临床医学院,南京军区福州总医院神经外科,福州 350025)
摘要:
目的:探讨过氧化物酶体增殖物激活受体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(10-7、10-6、10-5 mol/L)曲格列酮作用于GH3细胞,另设空白对照组(F-12培养液)和0.01%二甲亚砜(DMSO)培养组,应用四甲基偶氮唑蓝(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CyclinD1基因mRNA表达。结果:曲格列酮干预GH3细胞72 h后,可剂量依赖性抑制GH3细胞增殖,并使GH3细胞被明显阻滞于G1/S期,CyclinD1 mRNA表达较对照组明显减少(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,可能与其结合PPAR-γ后导致CyclinD1 mRNA表达减少,细胞阻滞于G1期,促进肿瘤细胞死亡有关。
关键词:  垂体腺瘤  过氧化物酶体增殖物激活受体γ  曲格列酮  GH3细胞  细胞增殖
DOI:10.3724/SP.J.1008.2008.01052
投稿时间:2008-05-26修订日期:2008-06-02
基金项目:
Troglitazone inhibits proliferation of GH3 cell in vitro
CHEN Fu-yong,WANG Shou-sen*,WANG Shui-liang,WANG Ru-mi
(Department of Neurosurgery,Fuzhou General Hospital,Clinical College of Fujian Medical University,Fuzhou 350025,China)
Abstract:
Objective:To study the anti-proliferation effects of thiazolidinedione compounds-troglitazone, which is a high affinity ligand of PPAR-γ , on rat pituitary adenoma GH3 cell line and explore the related mechanisms.Methods: GH3 cells were separately treated with troglitazone (10-7,10-6 and 10-5 mol/L), dimethyl sulfoxide (DMSO) (DMSO control group) and phenol red- and serum-free F-12 medium (blank group). MTT was used to examine the cell growth in each group and FACS was used to detect the distribution of cell cycle. Semi-quantitative RT-PCR method was utilized to determine the expression of CyclinD1 mRNA. ANOVA was used for statistical analysis.Results:The 72 h treatment with troglitazone inhibited GH3 cell proliferation in a dose-dependent manner. The treatment also induced cell cycle arrest in G1/S phase and significantly decreased the expression of CyclinD1 mRNA as compared to the other 2 groups (P<0.05).Conclusion:Troglitazone can obviously inhibit the proliferation of GH3 cells; the molecular mechanism may be the decrease of CyclinD1 mRNA due to binding to PPAR-γ.
Key words:  pituitary adenoma  peroxisome proliferator-activated receptor γ,thiazolidinedione compounds  troglitazone  GH3 cell  cell proliferation