LY294002对多发性骨髓瘤细胞增殖的抑制作用及机制研究

发布时间：2018-10-11 14:06

【摘要】：目的:探讨2-(4-吗啉基)-8-苯基-4氢-1-苯并吡喃-4酮(LY294002)对多发性骨髓瘤细胞株U266的增殖抑制作用及其机制。方法:用不同浓度(0、5、10和20μmol/L)LY294002处理U266细胞24、48和72 h后,MTT法检测细胞活力,吖啶橙染色法检测细胞形态,流式细胞术检测细胞周期,Western blot检测细胞中B淋巴细胞瘤-2(BCL-2)、BCL-2相关X蛋白(BAX),细胞周期蛋白D1(Cyclin D1),Cyclin E表达及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)通路的激活状况。结果:0、5、10和20μmol/L的LY294002处理U266细胞24、48和72 h后,能显著提高细胞增殖抑制率,并具有时间及剂量依赖性(r=0.408,r=0.485)。5,10,20μmol/L的LY294002处理细胞48 h,能使细胞核呈现致密浓染,细胞周期明显阻滞在G1期(P0.01),显著下调BCL-2,Cyclin D1,Cyclin E,PI3K及p-AKT表达(P0.01),明显上调BAX表达(P0.01)。结论:LY294002能显著抑制多发性骨髓瘤细胞U266增殖,其作用机制可能与抑制PI3K/AKT信号通路的激活有关。
[Abstract]:Aim: to investigate the inhibitory effect of 2- (4-morpholinyl) -8-phenyl-4-hydro-1-benzopyran-4-one (LY294002) on the proliferation of multiple myeloma cell line U266 and its mechanism. Methods: U266 cells were treated with 10 and 20 渭 mol/L LY294002 at different concentrations for 48 and 72 hours. The viability of U266 cells was detected by MTT and the morphology of U266 cells was detected by acridine orange staining. Flow cytometry was used to detect the expression of Cyclin D1), Cyclin E and the activation of phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) pathway in B lymphocytoma 2 (BCL-2), BCL-2 associated X protein (BAX), (BAX),) cells. Results: the proliferation inhibition rate of U266 cells was significantly increased after treatment with 10 渭 mol/L and 20 渭 mol/L LY294002 for 48 and 72 h, in a time and dose-dependent manner. The cells were treated with 5 渭 mol/L LY294002 for 48 h, and the cell nuclei were densified and stained in a dose-dependent manner. The cell cycle was significantly blocked in G1 phase (P0.01), and the expression of PI3K and p-AKT in BCL-2,Cyclin D1cyclin E was significantly down-regulated (P0.01), and the expression of BAX was upregulated (P0.01). Conclusion: LY294002 can significantly inhibit the proliferation of multiple myeloma cell line U266, and its mechanism may be related to the inhibition of activation of PI3K/AKT signaling pathway.
【作者单位】：张家口学院医学基础部;张家口学院护理学院;
【分类号】：R733.3

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