[关键词]
[摘要]
目的:观察过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptorγ , PPARγ)激动剂曲格列酮(troglitazone, TGZ)对垂体腺瘤细胞生长和生长激素(growth hormone,GH)分泌的影响,并探讨其可能的作用机制。方法:采用MTT和ELISA法检测TGZ对大鼠垂体腺瘤细胞系GH3细胞增殖和GH分泌的抑制效应,进一步应用电镜、FCM及Western blotting分别检测细胞凋亡、细胞周期以及Caspase3、Bcl2和Bax蛋白的表达。结果:TGZ呈剂量和时间依赖性方式抑制GH3细胞的增殖和GH的分泌;TGZ干预后的GH3细胞出现典型的凋亡形态特征; TGZ干预GH3细胞后,G2、S期的细胞比例下降,而G1期的细胞比例明显增加;Bax和Caspase3蛋白表达水平明显增加,而Bcl2蛋白表达水平下调,且表现出剂量依赖效应。结论:PPARγ激动剂TGZ可能通过诱导细胞凋亡和阻滞细胞周期来抑制垂体腺瘤细胞生长及其生长激素分泌。
[Key word]
[Abstract]
Objective:To examine the effects of troglitazone (TGZ), agonist of peroxisome proliferatoractivated receptorγ (PPARγ), on the growth and growth hormone (GH) secretion of pituitary adenoma cells, and to expolre the possible mechanism. Methods: The inhibitory effect of TGZ on the proliferation and GH secretion of rat pituitary adenoma cell line GH3 was detected by MTT assay and ELISA. Furthermore, apoptosis, cell cycle as well as caspase3, Bcl2 and Bax expression of GH3 cells were examined by transmission electron microscopy, flow cytometry and Western blotting, respectively. Results: TGZ dose and timedependently inhibited the proliferation and GH secretion of GH3 cells. GH3 cells treated with TGZ had a typical morphological characteristic of apoptosis. CH3 cell number in G1 phase was increased and cell number in G2, S phases was significantly decreased after treatment with TGZ. The expression of caspase3 and Bax in CH3 cells was significantly increased and Bcl2 expression was markedly decreased in a dosedependent manner after treatment with TGZ. Conclusion: PPARγ agonist inhibits the growth and GH secretion of pituitary adenoma cells through inducing apoptosis and cell cycle arresting.
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[基金项目]
海南省自然科学基金资助项目(No.30852)