目的：研究辛二酰苯胺异羟肟酸（suberoylanilide hydroxamic acid, SAHA）对结肠癌细胞系HCT116和SW480增殖、周期和凋亡的影响，并对其分子作用机制进行初步探讨。 方法： 将不同浓度SAHA分别处理结肠癌HCT116和SW480细胞后，MTT法检测SAHA 对HCT116和SW480细胞增殖的影响，流式细胞仪检测HCT116和SW480细胞周期和细胞凋亡率，罗丹明（rhodamine) 123 和二氯二氢荧光素二乙酸酯（DCFH-DA）法检测HCT116和SW480细胞线粒体跨膜电位（ΔΨm）和活性氧（ROS）水平，Real-time PCR和Western blotting法检测乙酰化组蛋白3（Ac-H3）、p21、Cyclin D1、Bax和Bcl-2的mRNA和蛋白的表达水平。 结果： SAHA作用于HCT116和SW480细胞48 h后，细胞增殖被抑制、细胞周期G1期比率升高、凋亡率升高（均P<0.05）,线粒体跨膜电位显著下降、细胞内ROS产生增多（均P<0.05）。与对照组比较，SAHA处理组p21和Bax mRNA增多、Cyclin D1和Bcl-2 mRNA表达量减少（均P<0.05），相关蛋白Ac-H3、p21和Bax增多，Cyclin D1和Bcl-2减少（均P<0.05）。 结论： SAHA抑制结肠癌HCT116和SW480细胞增殖、阻滞细胞周期并诱导细胞凋亡，其机可能与调节p21、CyclinD1 和Bcl-2家族基因的表达、促进组蛋白乙酰化有关。

Objective:To investigate the effects and molecular mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) on the proliferation, cell cycle and apoptosis of colon cancer HCT116 and SW480 cells. Methods: Colon cancer cells (HCT116 and SW480) were treated with a series of concentrations of SAHA．MTT assay was em-ployed to evaluate the effect of SAHA on proliferation of HCT116 and SW480 cells．The cell cycle distribution and apoptosis were determined by flow cytometry．Rhodamine 123 and DCFH-DA were applied to detect the mito-chondrial membrane potential(ΔΨm) and reactive oxygen species (ROS) production．Reverse transcription poly-merase chain reaction (RT-PCR) and Western blotting were used to assess the mRNA and protein expressions of Ac-H3, p21, Cyclin D1, Bax and Bcl-2. Results: After 48 h of SAHA treatment on HCT116 and SW480 cells, the cell proliferation was inhibited，the G1 phase ratio of cells and the apoptosis rate was increased (all P<0.05); moreover,SAHA also reduced ΔΨm and increased cellular ROS production (all P<0.05). Compared with control group, the mRNA expressions of p21 and Bax were higher in SAHA group, while the mRNA expressions of CyclinD1 and Bcl-2 were lower (all P<0.05); Furthermore, the protein expressions of Ac-H3，p21 and Bax were improved，while the protein expressions of CyclinD1 and Bcl-2 were decreased in SAHA group (all P<0.05). Conclusion: SAHA may suppress cell growth, induce apoptosis and cause cell cycle arrest of colon cancer cells by promoting histone acetyla-tion and modulating their related genes of p21, CyclinD1 and Bcl-2 family.

辽宁省教育厅科学技术一般资助项目（No.LJQ2014333)