研究组蛋白去乙酰化酶4（histone deacetyase 4，HDAC4）在人肝癌细胞株Bel7402中的表达，及其对Bel7402细胞增殖和分化的调控作用。方法: 培养Bel7402细胞,以组蛋白去乙酰化酶抑制剂苯丁酸钠（sodium phenylbutyrate，SPB）作用于Bel7402，RTPCR检测用药前后HDAC4 mRNA的表达水平，倒置相差显微镜观察细胞形态改变， MTT比色法观察SPB对Bel7402生长的抑制作用，流式细胞术分析细胞周期，免疫组化法观察Bel7402细胞P27蛋白的表达水平。结果: SPB处理后Bel7402中HDAC4 mRNA的表达水平降低(0.88±0.13,0.12±0.04,P<0.05)；SPB处理后Bel7402细胞生长受到明显抑制，且与SPB剂量和作用时间相关；同时细胞形态出现成纤维细胞样改变；细胞周期阻滞于G1期\[(50.6±4.0)%，（78.8±3.6）%, P<0.05)\]；P27蛋白表达水平增强（23±11, 61±7,P<0.05）。结论: SPB降低HDAC4在人肝癌细胞中的表达，从而诱导部分人肝癌细胞分化， 该作用与P27蛋白水平变化有关。

To investigate the expression of histone deacetyase4 (HDAC4) in human liver carcinoma cell line Bel7402 and to explore the regulatory effects of HDAC4 on the proliferation and differentiation of Bel7402. Methods: Carcinoma cells Bel7402 was treated with different concentrations of sodium phenylbutyrate (SPB), an inhibitor of HDAC4. Expression of HDAC4 mRNA in Bel7402 cells was analyzed by RTPCR before and after SPB treatment. Reverse microscope was used to observe the morphological changes of Bel7402 cells. MTT assay and flow cytometry were adopted to describe the proliferation and cell cycle of Bel7402 cells. Expression of P27 protein was determined by immunohistochemical method. The statistical analysis was performed using oneway ANOVA and student t test. Results: SPB significantly decreased the expression of HDAC4 in Bel7402\[(0.88±0.13) vs (0.12±0.04), P<0.05\]. It also inhibited the Bel7402 cell growth in a timeand dosedependent manner. Fibrous changes of Bel7402 cells was observed after SPB treatment. SPB treatment arrested cell at G1 phase \[(50.6±4.0)% vs (78.8±3.6)%, P<0.05\] and enhanced the expression of P27 in Bel7402 \[（23±11) vs (61±7),P<0.05\].Conclusion: SPB treatment can decrease the expression of HDAC4 in human liver cancer cell Bel7402 and subsequently inhibits proliferation of Bel7402 cells, which might be associated with the change of P27 protein expression.

山东省科技攻关基金资助项目（No.2005GG4402049）