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曲古抑菌素A对前列腺癌LNCaP细胞雄激素受体的清除作用 被引量:3

Depletion of androgen receptor in LNCaP prostate cancer cell line by trichostatin A
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摘要 目的:研究组蛋白去乙酰化酶抑制剂曲古抑菌素A(trichostatinA,TSA)对前列腺癌细胞的抑制作用机理。方法:四甲基偶唑氮蓝(MTT)检测药物对肿瘤细胞增殖的影响;Hochest33342染色观察细胞凋亡的形态学变化;Western印迹分析雄激素受体(AR)蛋白的表达;反转录PCR检测AR转录水平的变化。结果:TSA在较低浓度即能有效抑制LNCaP细胞的增殖,EC50为125.9nmol·L-1,并诱导肿瘤细胞凋亡;药物处理后细胞周期依赖性蛋白激酶抑制剂p21表达增高,AR呈时间及剂量依赖性被清除。TSA对AR的清除是发生在蛋白水平的降解,而不影响其转录。结论:TSA能够清除对细胞生长具有重要作用的AR细胞信号通路,从而对前列腺癌LNCaP细胞发挥抑制作用。 AIM: To investigate the mechanisms underlying the antitumor effect of trichostatin A (TSA) on LNCaP prostate cancer cell line. METHODS: Proliferation of LNCaP cells exposed to TSA was detected by MTF assay. Cell apoptosis was assayed by Hoechst 33342 nuclei staining. Western blotting was performed to analyze the expression of the androgen receptor (AR) 'after TSA exposure. Semiuantitative RT-PCR was used to assay the transcription changes of AR. RESULTS: TSA kills LNCaP cells with an ED50 value of 125.9 nmol· L^-1 with in 48 hours exposure. TSA inhibited LNCaP cell proliferation as well as inducing cell apoptosis. TSA depleted AR both in a close and time dependent manner. Moreover, the expression of cell cycle-dependent kinase inhibitor, p21, was induced. The decreasing of AR occurred at the protein level instead of transcription suppression. CON- CLUSIONS: TSA exhibits significant antitumor effect against LNCaP cells through depletion of AR.
出处 《中国临床药理学与治疗学》 CAS CSCD 2005年第11期1249-1252,共4页 Chinese Journal of Clinical Pharmacology and Therapeutics
基金 国家自然科学基金重点项目(№30330620)
关键词 前列腺肿瘤 受体 雄激素 细胞凋亡 组蛋白脱乙酰基酶 组蛋白去乙酰化酶抑制剂 曲古抑菌素A 细胞信号通路 prostatic neoplasms receptors, androgen apoptosis histone deacetylases histone deaeetylaseinhibitors trichostatin A cell signaling pathway
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参考文献10

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同被引文献18

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