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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。
Objective: To study the inhibitory mechanism of histone deacetylase inhibitor trichostatin A (TSA) on prostate cancer cells. METHODS: The effects of drugs on the proliferation of tumor cells were detected by MTT assay. Morphological changes of apoptosis were observed by Hochest33342 staining. The expression of androgen receptor (AR) protein was analyzed by Western blotting. Detection of AR transcriptional changes. Results: TSA at a low concentration could effectively inhibit the proliferation of LNCaP cells with EC50 of 125.9nmol·L-1, and induce apoptosis of tumor cells. The expression of cell cycle-dependent protein kinase inhibitor p21 increased after treatment with AR And dose-dependently cleared. The clearance of AR by TSA occurs at the protein level without affecting its transcription. Conclusion: TSA can clear the AR cell signaling pathway that plays an important role in cell growth and thus exert its inhibitory effect on prostate cancer LNCaP cells.