Vorinostat (SAHA) is a pan-histone deacetylase (HDAC) inhibitor (IC50=10 nM) with inhibitory activity against HDAC1/2/3/6/7/11. Vorinostat has antitumor activity, induces cell differentiation, blocks the cell cycle and induces apoptosis.

HDAC:~10 nM (cell free)

方法：滑膜肉瘤细胞 SW-982 和软骨肉瘤细胞 SW-1353 用 Vorinostat (0.5-15 μM) 处理 48 h，使用 MST assay 检测细胞活力。
结果：Vorinostat 以剂量依赖的方式抑制 SW-982 和 SW-1353 细胞增殖，IC50 分别为 8.6 μM 和 2.0 μM。[1]
方法：子宫肉瘤细胞 MES-SA 用 Vorinostat (3 μM) 处理 24-72 h，使用 Western Blot 方法检测靶点蛋白表达水平。
结果：在整个处理期间，HDAC1 的表达没有差异。HDAC2、3 和 7 显示出 Vorinostat 对表达的显著抑制。[2]

方法：为检测体内抗肿瘤活性，将 Vorinostat (50 mg/kg in HOP-β-CD) 腹腔注射给携带子宫肉瘤 MES-SA 的 Nude-Foxn1nu/nu 小鼠，每周五次，持续二十一天。
结果：与安慰剂组相比，Vorinostat 治疗组观察到肿瘤生长减少了 50% 以上。[1]
方法：为研究在真性红细胞增多症 (PV) 动物模型中的作用，将 Vorinostat (200 mg/kg in 50% PEG-400) 腹腔注射给 MxCre;Jak2V617F/+ 小鼠，每周五次，持续两周。
结果：Vorinostat 治疗使 Jak2V617F 敲除小鼠的外周血计数正常化，并显著减少脾肿大。Vorinostat 可能对 PV 和其他 JAK2V617F 相关的骨髓增生性肿瘤具有治疗潜力。[3]

Cells were plated onto 100-mm tissue culture plates at a density of 2 × 10^6 for 48 h and then treated with SAHA or equal concentrations of the vehicle. For longer drug exposure times, medium with drug or vehicle were exchanged every 48 h. For wash-out experiments, cells were treated with SAHA daily for 60–72 h (drug and medium were exchanged at 48 h), then SAHA was washed out and replaced with 10% FCS containing DMEM [3].

Athymic Nude-Foxn1nu/nu mice were used in the present study. They were housed at 22°C at a constant light-dark cycle (12-h light, 12-h dark) and had free access to water and rodent chow (4-5% fat, 21% protein). Twelve weeks old male mice (n = 14) were anesthetized with Isofluran and 5 × 10^6 MES-SA cells were injected subcutaneously into the right flank of the animal. Mice from a control group received placebo containing 300 μl of empty HOP-β-CD (2-hydroxypropyl-β-cyclodextrin) vesicles. Another group of mice received vorinostat dissolved in HOP-β-CD at a concentration of 50 mg/kg/day. Both, empty vesicles and vorinostat were administered intraperitoneally, starting on the day 4 after the injection of MES-SA tumor cells. Mice body weight and tumor size (w2 × l × 0.52; measured by caliper) were estimated twice a week. All mice were treated for 21 days and afterward sacrificed by cervical dislocation. Each tumor was isolated as a whole and different tumor parameters (weight, volume, size, and macroscopic appearance) were determined. Finally, tumor slices were cryopreserved and formalin fixed (4%) for further analyses [1].