罗格列酮对U937细胞生长抑制作用及其机制的探讨

Effect of rosiglitazone on proliferation of U937 cells and its mechanisms

目的:探讨过氧化物酶体增殖因子活化受体γ(PPARγ)配体罗格列酮(ROS)对人急性单核细胞白血病U937细胞生长抑制作用及其作用机制。方法:体外培养人急性单核细胞白血病U937细胞,应用不同浓度的罗格列酮处理人急性单核细胞白血病U937细胞,采用MTT比色法测定药物对细胞增殖的抑制作用;用流式细胞术、AnnexinⅤ/PI双染色法观察细胞凋亡率;并分析细胞周期改变;RT-PCR法分析PPARγmRNA表达。结果:ROS浓度>80μmol/L时,对U937细胞产生明显的增殖抑制作用,P<0.05;AnnexinⅤ/PI双染色法观察细胞凋亡率>50%,并将细胞周期阻滞在G1期,P<0.05;RT-PCR检测U937细胞中PPARγmRNA表达无明显变化。结论:ROS浓度>80μmol/L时,对U937细胞产生明显的增殖抑制作用及诱导凋亡作用,同时将细胞周期阻滞在G1期,但是PPARγmRNA表达无明显变化,推测可能与激活PPARγ表达无明显相关,可能存在另外的信号转导途径。

OBJECTIVE：To investigate the effects of rosiglitazone on human leukemic cell （U937） proliferation and its mechanisms.METHODS：After treated with rosiglitazone at different dosages,the cell cytotoxic effect was evaluated by MTT assay.The distribution of cell cycle and apoptosis was examined by flow cytometry （FCM）.The expression of PPAR-γ was examined by RT-PCR.RESULTS：Rosiglitazone inhibited the proliferation of U937 cells when the concentration was above 80 μmol/L （P〈0.05）;the apoptosis achieved above 50%.Rosiglitazone arrested the cell cycle in G1 phase （P〈0.05）;PPAR-γ expressed in U937 cells.The expressions of PPAR-γ tested by RT-PCR had no differences among the different groups.CONCLUSIONS：Rosiglitazone has the capabilities of inhibiting proliferation especially when the drug concentration is above 80 μmol/L,and arresting U937 cells at G1 phase of the cell cycle,but the expressions of PPAR-γ tested by RT-PCR have no differences among the different groups.So there are maybe other pathways correlated with the effects,not the activation of PPAR-γ.