Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (mainland).
Department of Emergency, Hunan Provincial Peoples' Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China (mainland).
Med Sci Monit. 2017 Dec 6;23:5793-5802. doi: 10.12659/msm.904597.
BACKGROUND Histone deacetylase (HDAC) inhibitors are emerging as a new class of anti-cancer drugs that promote cancer cell apoptosis, and include suberoylanilide hydroxamic acid (SAHA). The aim of this study was to investigate the mechanism of SAHA-induced apoptosis in human prostate cancer cell lines, DU145 and PC-3. MATERIAL AND METHODS Cell lines, DU145 and PC-3, were studied before and after treatment with SAHA. The effects of SAHA treatment on cell proliferation were studied using the MTT cell proliferation assay. Annexin-V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) staining were used to study the effects of SAHA treatment on cell apoptosis. Western blotting, quantitative polymerase chain reaction (qPCR) and short interfering (si)RNA assays were performed to study the effects of SAHA treatment on apoptotic and cell cycle proteins and the Akt/FOXO3a signaling pathway. RESULTS Treatment with SAHA inhibited cell proliferation in human prostate cancer cell lines DU145 and PC-3 cells in a dose-dependent way. Cell cycle analysis and Annexin-V FITC/PI staining showed that treatment with SAHA resulted in G2/M cell cycle arrest and increased cell apoptosis in a dose-dependent way. Also, treatment with SAHA reduced the protein expression levels cyclin B and cyclin A2 and promoted the activation of FOXO3a by inhibiting Akt activation. Western blotting, the siRNA assay, and qPCR showed that FOXO3a, the Bcl-2 family of proteins, survivin, and FasL were involved in SAHA-induced apoptosis in prostate cancer cells grown in vitro. CONCLUSIONS Treatment with SAHA promoted apoptosis via the Akt/FOXO3a signaling pathway in prostate cancer cells in vitro.
组蛋白去乙酰化酶（HDAC）抑制剂作为一种新型的抗癌药物，可促进癌细胞凋亡，其中包括丁酸钠（SAHA）。本研究旨在探讨 SAHA 诱导人前列腺癌细胞系 DU145 和 PC-3 细胞凋亡的机制。
在 SAHA 处理前后研究了细胞系 DU145 和 PC-3。使用 MTT 细胞增殖测定法研究 SAHA 处理对细胞增殖的影响。用 Annexin-V-荧光素异硫氰酸酯（FITC）和碘化丙啶（PI）染色研究 SAHA 处理对细胞凋亡的影响。通过 Western blot、定量聚合酶链反应（qPCR）和短发夹 RNA（siRNA）实验研究 SAHA 处理对凋亡和细胞周期蛋白及 Akt/FOXO3a 信号通路的影响。
SAHA 处理以剂量依赖性方式抑制人前列腺癌细胞系 DU145 和 PC-3 细胞的增殖。细胞周期分析和 Annexin-V FITC/PI 染色显示，SAHA 处理导致 G2/M 细胞周期阻滞，并以剂量依赖性方式增加细胞凋亡。此外，SAHA 处理通过抑制 Akt 激活降低了细胞周期蛋白 B 和细胞周期蛋白 A2 的蛋白表达水平，并促进了 FOXO3a 的激活。Western blot、siRNA 实验和 qPCR 显示，FOXO3a、Bcl-2 家族蛋白、survivin 和 FasL 参与了体外培养的前列腺癌细胞中 SAHA 诱导的凋亡。
SAHA 通过 Akt/FOXO3a 信号通路促进前列腺癌细胞的凋亡。
