CXCR4抑制剂 AMD3100联合硼替佐米对人淋巴瘤细胞株 Ramos 增殖、凋亡的影响

摘要

Objective To investigate the synergistic effects of CXCR4 inhibitors AMD3100 and Bortezomib on apoptosis of lymphoma cell lines Ramos. Methods ①The detection of CXCR4 and NF - κB on bone marrow mononuclear cells of lymphoma patients;②The cells were trea-ted with AMD3100,Bortezomib,AMD3100 combined with Bortezomib,respectively. The proliferation was estimated by CCK - 8,the cell apopto-sis was analysed by flow cytometry,the expression level of NF - κB,Bcl - 2,Bcl - xl,c - IAP1 and Caspase - 3 were measured by Western blot. Results ①The CXCR4 and NF - κB were both highly expressed in bone marrow mononuclear cells of lymphoma patients. ②Both AMD3100 and Bortezomib can inhibit the proliferation and promote apoptosis of Ramos cell,the effect showed dosage dependent manner,AMD3100 and Borte-zomib had the synergy effects( P ﹤ 0. 05). ③The expression level of NF - κB,Bcl - 2,Bcl - xl and c - IAP1 were lower in the single drug and combination groups,but the expression of Caspase - 3 was in the different way. Conclusion AMD3100 and Bortezomib has synergistic effect in the proliferation and apoptosis of Ramos cell line,the mechanism of the effects may be down - regulated the expression level of NF - κB,Bcl - 2, Bcl - xl,c - IAP1and up - regulated the expression of Caspase - 3.%目的：探讨 CXCR4抑制剂 AMD3100、硼替佐米对人淋巴瘤细胞株 Ramos 协同诱导凋亡作用。方法①检测淋巴瘤患者骨髓单个核细胞中 CXCR4及核因子κB（NF -κB）表达水平；②AMD3100、硼替佐米单用以及联合用药分别处理 Ramos 细胞，利用 CCK -8法检测细胞增殖；利用流式细胞术检测细胞凋亡；Wester blot 检测 NF -κB、Bcl -2、Bcl - xl、c - IAP1及 Caspase -3表达水平。结果①淋巴瘤患者骨髓单个核细胞中 CXCR4、NF -κB 表达增高；②AMD3100、硼替佐米作用 Ramos 细胞后，随着药物浓度的增加，对细胞增殖的抑制作用逐渐增强、凋亡增加，两药具有协同作用（ P ﹤0.05）；③AMD3100、硼替佐米单药组 NF -κB、Bcl -2、Bcl - xl 及 c - IAP1表达降低，Caspase -3表达升高，联合用药组作用增强。结论 AMD3100、硼替佐米对 Ramos 细胞的增殖抑制、凋亡促进具有协同作用，其作用机制可能是通过抑制 NF -κB、Bcl -2、Bcl - xl、c - IAP1及增强 Caspase -3表达。