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目的观察12-氧-十四烷酰醇-13-乙酸酯(TPA)和三氧化二砷(As2O3)联合应用对白血病细胞凋亡有无协同作用,并初步探讨其诱导凋亡的机制,为As2O3和TPA联合用于白血病的治疗提供理论依据。方法采用不同浓度的As2O3联合TPA作用于人白血病细胞系HL-60,用MTT法检测细胞增殖,用TUNEL法检测细胞凋亡,分析不同浓度的As2O3联合TPA对HL-60细胞增殖和凋亡的影响。c-jun氨基末端激酶(JNK)检测法检测JNK活性。结果TPA联合2.0×10-6mol/L的As2O3对HL-60细胞增殖抑制作用明显增强,抑制程度大于单用As2O3组(P<0.05)。2.0×10-6mol/L As2O3组诱导HL-60细胞发生凋亡的比率高于对照组,而TPA联合2.0×10-6mol/LAs2O3组引起的细胞凋亡率高于单用As2O3组(P均<0.05)。TPA和As2O3均能激活JNK,且二者有协同作用。结论TPA增强As2O3抑制HL-60细胞增殖和促进凋亡的作用,以上体外实验结果为TPA和As2O3联合用药治疗难治/复发性白血病提供了理论依据。
Objective To investigate the synergistic effect of 12-oxo-tetradecanol-13-acetate (TPA) and arsenic trioxide (As2O3) on the apoptosis of leukemia cells and to explore the mechanism of apoptosis induced by As2O3 and TPA combined for the treatment of leukemia provide a theoretical basis. Methods Different concentrations of As2O3 and TPA were applied to human leukemia cell line HL-60. Cell proliferation was measured by MTT assay. Cell apoptosis was detected by TUNEL assay. The effects of different concentrations of As2O3 and TPA on proliferation and apoptosis of HL-60 cells influences. JNK activity was detected by c-jun Amino-Terminal Kinase (JNK) assay. Results TPA combined with 2.0 × 10-6mol / L As2O3 significantly inhibited the proliferation of HL-60 cells, and the inhibitory effect was greater than that of As2O3 alone (P <0.05). The apoptosis rate of HL-60 cells induced by 2.0 × 10-6mol / L As2O3 was higher than that of the control group, while the apoptosis rate of TPA combined with 2.0 × 10-6mol / LAs2O3 group was higher than that of the cells treated with As2O3 alone <0.05). Both TPA and As2O3 activate JNK, and both have synergistic effects. Conclusion TPA enhances the effect of As2O3 on the proliferation and apoptosis of HL-60 cells. The above results provide theoretical basis for the combination of TPA and As2O3 in the treatment of refractory / relapsed leukemia.