目的： 观察组蛋白乙酰基转移酶（histone deacetylase，HDAC）抑制剂曲古抑菌素A（trichostatin A，TSA）对子宫内膜癌Ishikawa细胞凋亡的影响，并研究其与Krupell样因子4（Krupell-like factor 4，KLF4）的关系。 方法： 0、50、100、200、300、500 ng/ml TSA作用于Ishikawa细胞24 h，或100 ng/ml TSA作用于Ishikawa细胞0、4、8、12、24、48 h，流式细胞术检测Ishikawa细胞凋亡情况，qRT-PCR检测Ishikawa细胞中KLF4 mRNA的表达情况；将KLF4真核表达载体pcDNA3-KLF4转染Ishikawa细胞，流式细胞术检测Ishikawa细胞凋亡情况。 结果： 100 ng/ml TSA作用于Ishikawa细胞 24 h后，Ishikawa细胞的凋亡率显著高于对照组\[（30.6±4.5）%vs（7.53±0.93）%，P＜0.05\]；不同质量浓度TSA处理Ishikawa细胞24 h后或100 ng/ml TSA作用Ishikawa细胞不同时间后，KLF4 mRNA表达水平以剂量依赖和时间依赖方式明显增高（P<0.05）；pcDNA3-KLF4转染后Ishikawa细胞凋亡率显著增加\[（27.3±2.7）%vs（4.53±1.75）%，P＜0.05\]。 结论： TSA能通过诱导子宫内膜癌Ishikawa细胞中KLF4的表达，促进Ishikawa细胞发生凋亡。

Objective : To observe the effect of Trichostatin A (TSA) on the apoptosis of endometrial cancer Ishikawa cells and to study its relationship with Krupell-like-factor 4 (KLF4) in this course. Methods: Ishikawa cells were cultured with different concentrations of TSA 0, 50, 100, 200, 300, 500 ng/ml for 24 h or 100 ng/ml TSA for 0, 4, 8, 12, 24 and 48 h. FACS and qRT-PCR were used to detect apoptosis and KLF4 mRNA level, respectively. Results: The apoptosis rate was increased compared to the control in the Ishikawa cells treated with 100 ng/ml TSA for 24 h （\[30.6±45\]%vs \[7.53±0.93\]%, P<0.05). The mRNA levels of KLF4 were up-regulated after Ishikawa cells were stimulated with different concentrations of TSA for 24 h or with 100 ng/ml TSA for 4, 8, 12, 24, 48 h (P<0.05). Those effects were in a dose-dependent or time-dependent manner. The apoptosis rate was increased compared to the control in the Ishikawa cells over-expressed KLF4 （\[27.3±27\]% vs \[4.53±1.75\]%, P<0.05). Conclusion: TSA induces apoptosis of Ishikawa cells by up-regulating the expression of KLF4.

国家重点基础研究发展计划（973计划）资助项目（No. 2010CB529905）