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目的：研究组蛋白去乙酰化酶(HDAC)抑制剂FK228诱导前列腺癌细胞系DU145凋亡的作用机制。方法：MTT比色法测定FK228抑制DU145细胞增殖及其对细胞的杀伤效应；瑞氏-姬姆萨染色观察细胞形态的变化；流式细胞术分析细胞周期的改变；蛋白印迹实验检测细胞内蛋白表达水平的变化。结果：FK228明显抑制DU145细胞体外增殖,并介导细胞死亡；12．5 ng/ml FK228作用细胞48 h后,细胞存活率降至63．7%；伴有细胞形态改变及细胞周期阻滞于G_0/G_1期；细胞内多种重要的激酶蛋白,包括EGFR、Her2、RM-1、Sic、Cdk4、Akt及凋亡抑制蛋白Survivin均发生了不同程度的降解,细胞内两条重要的生存信号通路Raf-MEK-ERK及PI3K/Akt被阻断,细胞发生凋亡。结论：FK228可以通过清除细胞内重要信号蛋白、阻断细胞生存信号通路来诱导DU145细胞发生凋亡。
AIM: To investigate the mechanism of histone deacetylase (HDAC) inhibitor FK228 in inducing apoptosis of prostate cancer cell line DU145. Methods: MTT assay was used to determine the effect of FK228 on DU145 cell proliferation and its cytotoxicity. Wright-Giemsa staining was used to observe the changes of cell morphology. Flow cytometry was used to analyze cell cycle changes. Western blotting was used to detect intracellular protein Changes in expression levels. RESULTS: FK228 significantly inhibited the proliferation of DU145 cells in vitro and induced cell death. After 48 h of 12.5 ng / ml FK228 treatment, the cell viability decreased to 63.7%; accompanied with cell morphological changes and cell cycle arrest G_0 / G_1 phase. A variety of important kinase proteins, including EGFR, Her2, RM-1, Sic, Cdk4, Akt and Survivin, all degraded to some extent. Two important intracellular survival signals Pathway Raf-MEK-ERK and PI3K / Akt is blocked, the cell apoptosis. Conclusion: FK228 can induce apoptosis of DU145 cells by removing important signaling proteins in cells and blocking the signal transduction pathways of cell survival.