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 Bortezomib( 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 observed. 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 24-72 h 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.
出处
《解放军医药杂志》
CAS
2015年第3期50-54,共5页
Medical & Pharmaceutical Journal of Chinese People’s Liberation Army
基金
国际合作专项基金(2011DFA32820)
国家自然科学基金(81460037)