Tumor angiogenesis is closely related to tumor development, immune escape, and drug resistance. Therefore, the development of effective anti-tumor angiogenesis drugs is of great research significance. Although the current clinical angiogenesis inhibitors have achieved certain efficacy, they also pose the problems of limited and short duration of efficacy, drug resistance, and intrinsic toxicity. Anti-tumor angiogenesis strategies targeting endothelial cells (ECs) have attracted widespread attention in the development of highly effective and low toxicity anti-angiogenesis inhibitors. Studies have verified that the trace element selenium (Se) can inhibit tumor growth by inhibiting tumor angiogenesis through different mechanisms. Nevertheless, it is unclear whether Se speciation has different effects on anti-tumor angiogenesis. Herein, we found that Se exhibited effective anti-angiogenic activity, and its mechanisms of activity were determined by its chemical speciation. Organic Se can significantly inhibit tumor angiogenesis by targeting thioredoxin reductase (TrxR) to trigger cell apoptosis and cell cycle arrest and by increasing reactive oxygen species (ROS) production in ECs. Inorganic Se can induce cell cycle arrest and increase ROS production in ECs, showing promising anti-angiogenic effects. Se nanoparticles (SeNPs) slightly inhibit tumor angiogenesis by inducing apoptosis and cell cycle arrest and by increasing the production of ROS. In summary, this study elucidates the anti-angiogenic activity of Se speciation control with a view to providing a scientific reference for the design and development of novel Se-based highly effective and low toxicity angiogenesis inhibitors.

肿瘤血管生成与肿瘤发生、免疫逃逸、耐药等密切相关。因此，开发有效的抗肿瘤血管生成药物具有重要的研究意义。目前临床上的血管生成抑制剂虽然取得了一定的疗效，但也存在药效有限、持续时间短、耐药性和内在毒性等问题。针对内皮细胞（EC）的抗肿瘤血管生成策略在开发高效、低毒的抗血管生成抑制剂方面引起了广泛关注。研究证实，微量元素硒（Se）可以通过不同机制抑制肿瘤血管生成，从而抑制肿瘤生长。然而，尚不清楚硒的形态是否对抗肿瘤血管生成有不同的影响。在此处，我们发现硒表现出有效的抗血管生成活性，其活性机制由其化学形态决定。有机硒可以通过靶向硫氧还蛋白还原酶（TrxR）触发细胞凋亡和细胞周期停滞以及增加内皮细胞中活性氧（ROS）的产生来显着抑制肿瘤血管生成。无机硒可以诱导细胞周期停滞并增加 EC 中 ROS 的产生，显示出有前景的抗血管生成作用。Se 纳米颗粒 (SeNP) 通过诱导细胞凋亡和细胞周期停滞以及增加 ROS 的产生来轻微抑制肿瘤血管生成。总之，