As2O3联合Aspirin对诱导肝癌细胞凋亡的影响

目的:观察As2O3与Aspirin联合应用对肝癌细胞Bel-7402的影响,并探讨其作用机制.方法:体外培养肝癌Bel-7402细胞,Aspirin、As2O3不同浓度孵育细胞.倒置显微镜观察细胞形态学改变,四甲基偶氮唑蓝(MTT)法检测As2O3和Aspirin单独及联合应用对Bel-7402细胞增殖情况的影响,流式细胞术观察细胞凋亡情况,并通过流式软件分析细胞周期变化.结果:As2O3及Aspirin对肝癌Bel-7402细胞生长均呈不同程度的抑制,且呈浓度依赖性.二者联合具有协同作用,药物联用组抑制率均显著高于单独应用同等剂量As2O3组和Aspirin组(P<0.05).2.0μmol/LAs2O3与0.2mmol/LAspirin联用组与2.0μmol/LAs2O3单药组相比,凋亡率从5.64%±0.56%提高到7.35%±0.62%,差异具有统计学意义(P<0.05).且通过对两组细胞周期检测发现,G1期细胞从40.52%±0.64%下降到32.03%±0.97%,G2期及S期细胞分别从9.57%±0.82%、50.41%±0.32%上升到13.66%±0.82%、54.37%±0.69%,Aspirin能显著增强As2O3诱导细胞集中于S及G2期的作用,从而增强其促凋亡作用.结论:Aspirin能增强As2O3诱导细胞凋亡的作用,该作用可能与影响细胞周期有关.

Aspirin enhances arsenic trioxide-induced apoptosis of hepatocarcinoma cells

AIM:To investigate the effect of aspirin combined with arsenic trioxide(As2O3) on human hepatocarcinoma cell line Bel-7402 and to explore the possible mechanisms involved.METHODS:Cultured Bel-7402 cells were incubated with different concentrations of aspirin and As2O3,alone or in combination.After treatment,cell morphology was observed using an inverted microscope,cell proliferation was determined by MTT assay,cell apoptosis was measured by flow cytometry with annexin V/propidium iodide staining,and cell cycle progression was analyzed by fluorescence-activated cell sorting.RESULTS:As2O3 and aspirin showed different degrees of inhibitory effect on the growth of Bel-7402 cells,and both were concentrationdependent.The two drugs had a synergistic effect,and the inhibitory effect in the combination group was more significant than those in thetwo monotherpay groups(both P < 0.05).Compared to treatment with 2.0 μmol/L As2O3 alone,treatment with 2.0 μmol/L As2O3 combined with 0.2 mmol/L aspirin significantly increased the apoptosis rate(5.64% ± 0.56% vs 7.35% ± 0.62%,P < 0.05),decreased the percentage of cells in G1 phase(0.52% ± 0.64% vs 32.03% ± 0.97%),and increased the percentages of cells in G2 phase or S phase(9.57% ± 0.82% vs 13.66% ± 0.82%,50.41% ± 0.32% vs 54.37% ± 0.69%).CONCLUSION:Aspirin enhances As2O3-induced apoptosis of Bel-7402 cells possibly by altering cell cycle progression.