Arsenic trioxide (ATO) has been shown to have antitumor effect in different tumors, although the underlying mechanisms are not fully understood. Autophagy plays a critical role in tumorigenesis and cancer therapy and has been found to be activated by ATO in different cells. However, the role of autophagy in the antitumor effect of ATO has not yet been elucidated. In this study, we investigated the role of autophagy in the antiangiogenic effect of ATO in human umbilical vein endothelial cells (HUVECs) in vitro and its underlying mechanism. Our data showed that ATO suppresses angiogenesis and induces autophagy in HUVECs through upregulation of forkhead box protein O3 (FoxO3a). Co‐incubated with autophagy inhibitor or knockdown of FoxO3a effectively inhibited ATO‐induced autophagy and reversed the antiangiogenic effect of ATO, indicating that ATO‐induced autophagy plays an antiangiogenic role in HUVECs. Our results highlight the importance of autophagy in the antiangiogenic effect of ATO and provide an improved understanding of the function of ATO.

中文翻译：

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FoxO3a调节自噬对三氧化二砷在HUVECs中的抗血管生成作用

三氧化二砷（ATO）已被证明在不同的肿瘤中具有抗肿瘤作用，尽管其潜在机制尚不完全清楚。自噬在肿瘤发生和癌症治疗中起着至关重要的作用，并且已被ATO在不同细胞中激活。但是，自噬在ATO抗肿瘤作用中的作用尚未阐明。在这项研究中，我们调查了自噬在人脐静脉内皮细胞（HUVEC）体外ATO抗血管生成作用中的作用及其潜在机制。我们的数据表明，ATO通过上叉前叉蛋白O3（FoxO3a）的上调抑制HUVEC中的血管生成并诱导自噬。与自噬抑制剂共同孵育或敲除FoxO3a可有效抑制ATO诱导的自噬并逆转ATO的抗血管生成作用，表明ATO诱导的自噬在HUVEC中起着抗血管生成的作用。我们的结果突出了自噬在ATO抗血管生成作用中的重要性，并提供了对ATO功能的更好的理解。