The indulgent success of arsenic trioxide (ATO) in the induction of complete remission in acute promyelocytic leukemia (APL) patients has accommodated this agent into the therapeutic protocols. However, the intrusion of unfavorable side effects had put an unanswered question on the way of the application of this agent; whether the benefits of ATO may outweigh its drawbacks. In this study, we found that when ATO is accompanied by an activator of peroxisome proliferator-activated receptors gamma (PPARγ), even the lower concentrations could induce significant inhibitory effects on the survival of NB4 through diminishing the ability of the cells to replicate DNA in the S phase of cell cycle. We also found that through suppression of the PI3K pathway, the combination of pioglitazone and ATO provided a signal through which the induction of apoptotic cell death was enhanced probably via the elevation of reactive oxygen species (ROS). With respect to the tight connection between PI3K pathway and autophagy system and given to the inhibitory effect of pioglitazone-plus-ATO on PI3K, we found that the combination of these agents not only suppressed the expression of autophagy-related genes, but also their efficacy was augmented when autophagy was inhibited in NB4; clarifying the encouraging role of autophagy in the survival maintenance of APL cells. In conclusion, given the significant efficacy as well as the safety profile of pioglitazone in potentiating the anticancer effects of chemotherapeutic drugs, the present study suggests it as a promising agent to be used in adjuvant strategy for the treatment of APL.

三氧化二砷（ATO）在诱导急性早幼粒细胞白血病（APL）患者完全缓解中取得的放纵成功使该药物适应了治疗方案。但是，不良反应的入侵使该药物的应用方式出现了未解决的问题。ATO的好处是否可能超过其缺点。在这项研究中，我们发现当ATO伴随着过氧化物酶体增殖物激活受体γ（PPARγ）的激活剂时，即使较低的浓度也可能通过降低细胞复制DNA的能力而对NB4的存活产生明显的抑制作用。细胞周期的S期。我们还发现，通过抑制PI3K途径，吡格列酮和ATO的组合提供了一个信号，可能通过增加活性氧（ROS）来增强凋亡细胞死亡的诱导。关于PI3K途径与自噬系统之间的紧密联系以及吡格列酮加ATO对PI3K的抑制作用，我们发现这些药物的组合不仅抑制了自噬相关基因的表达，而且还抑制了它们的功效。当NB4中的自噬被抑制时，其增加；阐明了自噬在APL细胞存活维持中的鼓励作用。总之，鉴于吡格列酮在增强化疗药物的抗癌作用方面具有显着的功效以及安全性，