阿司匹林与硼替佐米在多发性骨髓瘤细胞中相互作用的实验探讨

摘要

目的：探讨阿司匹林( ASA)联合硼替佐米( BTZ)在多发性骨髓瘤( MM)细胞中的相互作用及分子机制。方法以MM1. S与RPMI-8226细胞为研究对象,观察ASA、BTZ及ASA联合BTZ对MM细胞增殖与凋亡的影响,分析二者相互作用,并检测对Bcl-2、总Akt蛋白与磷酸化蛋白表达的影响。结果在24~72 h内,ASA组和BTZ组的细胞增殖抑制率均低于ASA+BTZ组(P<0．05),药物相互作用分析显示：二者存在相加作用；在药物处理48 h后,ASA组和BTZ组细胞凋亡率均低于ASA+BTZ组(P<0．05)；药物干预48 h后,ASA和BTZ组均下调Bcl-2蛋白表达,ASA+BTZ组则显著抑制Bcl-2蛋白水平(P<0．01,P<0．05)；药物干预48 h后,ASA组抑制p-Akt(Thr308)与p-Akt(Ser473)蛋白表达(P<0．05),BTZ组上调p-Akt(Thr308)蛋白表达水平(P<0．05),而ASA+BTZ组则明显抑制p-Akt(Thr308)与 p-Akt(Ser473)蛋白表达(P<0．05),但对总Akt水平无影响(P>0.05)。结论 ASA具有增强BTZ的抗MM作用,其机制可能为通过下调Bcl-2表达与抑制BTZ诱导的Akt磷酸化。%Objective To explore the interaction and its molecular mechanisms of Aspirin (ASA) and Borte-zomib (BTZ) in multiple myeloma (MM) cells. Methods The MM1. S and RPMI-8226 cells were used in this study, and the effects of ASA, BTZ and ASA in combination of BTZ on cell proliferation and apoptosis in MM cells were ob-served. The interaction between ASA and BTZ was analyzed, and the effects on levels of Bcl-2 and total Akt protein and phosphorylated protein expression were detected. Results The inhibitory rates of cell proliferation treated within 24-72h in ASA and BTZ groups were lower than that in ASA and BTZ group (P<0. 05), and drug interactions analysis showed that the additive effect existed between ASA and BTZ;after treatment for 48 h, apoptotic rates in ASA and BTZ groups were lower than that in ASA and BTZ group (P<0. 05);after treatment for 48 h, Bcl-2 protein levels in MM cells were reduced in ASA and BTZ groups, while Bcl-2 protein level in ASA and BTZ group was significantly inhibited (P<0. 01, P<0. 05);expressions of p-Akt (Thr308) and p-Akt (Ser473) were inhibited only by ASA treatment (P<0. 05), but the p-Akt (Ser473) expression was increased only by BTZ treatment in MM cells (P<0. 05), while the expressions were significantly inhibited by ASA and BTZ treatments ( P <0. 05 ) , but there was no effect on the total Akt level ( P >0. 05). Conclusion ASA may enhance the effect of BTZ against MM cells possibly through reducing Bcl-2 expression and inhibiting AKT phosphorylation induced by BTZ.