小檗胺联合依鲁替尼对急性髓系白血病细胞增殖和调亡的作用研究

Effect of Berbamine Combined with Ibrutinib on the Proliferation and Apoptosis of Acute Myeloid Leukemia Cells

目的:探讨小檗胺(berbamine, BBM)与依鲁替尼(ibrutinib)两药联合对急性髓系白血病(AML)细胞增殖和凋亡的影响及其联合作用机制。方法:分别使用不同浓度BBM、依鲁替尼单药及两药联合处理AML细胞系,采用CCK-8法检测细胞的存活率,计算CI_(50);流式细胞术检测细胞凋亡情况,Western blot检测凋亡相关蛋白以及BTK相关分子蛋白的表达量。结果:联合用药组细胞活力明显降低,ED_(50)/ED_(75)/ED_(90)的联合指数均<1。联合用药组凋亡相关蛋白的表达显著上调,而p-BTK、p-AKT、CREB、GSK3β和BCL-XL的表达显著下调。结论:BBM与依鲁替尼能协同抑制AML细胞增殖并促进AML细胞的调亡。BBM与依鲁替尼可能通过p-BTK/p-AKT/CREB和GSK3β/BCL-XL信号通路发挥协同作用。

Objective: To investigate the effects of the combination of berbamine(BBM) and ibrutinib on the proliferation and apoptosis of acute myeloid leukemia(AML) cells and the mechanism of combined action.Methods: The AML cell lines were treated with BBM, ibrutinib and the combination of the two drugs respectively, CCK-8 method was used to detect the cell proliferation inhibition rate of each group and calculate the combination index(CI).The cell apoptosis in each group was detected by flow cytometry.Western blot was used to determine the expression of related proteins in each group.Results: The cell viability in the combination group was significantly reduced, and the CI value of ED_(50)/ED_(75)/ED_(90)<1.The expression of apoptotic related protein in the combination group was significantly up-regulated, while the expression of p-BTK, p-AKT, CREB, GSK3β and BCL-XL were significantly down-regulated.Conclusion: BBM and ibrutinib can synergistically inhibit the proliferation of AML cells and promote the apoptosis of AML cells.BBM and ibrutinib may play a synergistic effect through the p-BTK/p-AKT/CREB and GSK3β/BCL-XL signaling pathways.