姜黄素调节NB4细胞P53和组蛋白H3乙酰化抑制细胞增殖的研究

目的 研究姜黄素对NB4细胞组蛋白H3和非组蛋白P53的乙酰化和细胞增殖的作用，探讨姜黄素抗白血病机制。方法 应用小同浓度（50，25，12．5，6．25，3．125μmol／L）的姜黄素作用NB4细胞不同时间（0，4，8，12，24h），MTT法测定姜黄素对NB4细胞增殖的影响，Western blot法检测乙酰化组蛋白H3和乙酰化P53的水平。结果 姜黄素以时间和剂量依赖方式抑制NB4细胞增殖，在24h和36h的IC值分别为40μmol／L和25μmol／L；能明显上调组蛋白H3的乙酰化水平，促进P53的表达和P53的乙酰化。结论 姜黄素具有去乙酰化酶抑制剂作用，能上调组蛋白H3乙酰化水平，促进肿瘤抑制凶子P53表达和活化，抑制白血病细胞增殖。

Effects of curcumin on the acetylation of histone H3, P53 and the proliferation of NB4 cells

OBJECTIVE: To investigate the effects of curcumin on the acetylation of histone H3, P53 and the proliferation of NB4 cells. METHODS: The total protein was extracted from NB4 cells treated without or with different concentrations of curcumin ( 50, 25, 12.5, 6.25 and 3.125 micromol/L) for different time (0, 4, 8, 12, 24 h). Western blot analysis was performed to determine the levels of acetylated histone H3, P53 and acetylated P53. MTT assay was performed to examine the growth inhibition effect of curcumin on NB4 cells. RESULTS: Curcumin could inhibit the proliferation of NB4 cells in a time- and dose- dependent manner, with the IC50 at 24 h and 36 h of 40 micromol/L and 25 micromol/L, respectively. The levels of histone H3 acetylation, P53 expression and P53 acetylation were increased obviously. CONCLUSION: Curcumin functions as a deacetylase inhibitor,which could increase the level of acetylated histone H3, enhance the expression and activity of tumor suppressor P53, and inhibit the proliferation of NB4 cells.