低氧，作为肿瘤微环境的重要标志，是氧化应激的主要原因，并在包括胶质母细胞瘤在内的各种恶性肿瘤中发挥了中心作用。低氧微环境中升高的活性氧（ROS）促进胶质母细胞瘤进展；然而，其潜在机制尚未明确。在此，我们发现低氧促进ROS的产生以及胶质母细胞瘤细胞的增殖、迁移和侵袭，但此促进受到ROS清除剂N-乙酰-L-半胱氨酸（NAC）和二苯基碘化铵（DPI）的抑制。低氧引起的ROS激活低氧诱导因子-1α（HIF-1α）信号，通过上皮- 间充质转化（EMT）增强细胞迁移和侵袭。此外，在低氧情况下丝氨酸蛋白酶抑制剂家族E成员1（SERPINE1）的诱导是ROS依赖的，且HIF-1α通过结合SERPINE1启动子区域介导ROS诱导SERPINE1的增加，从而促进胶质母细胞瘤的迁移和侵袭。综上所述，我们的数据显示低氧引起的ROS通过驱动HIF-1α-SERPINE1信号通路来加强胶质母细胞瘤的低氧适应性，并且靶向ROS可能是治疗胶质母细胞瘤的有前途的策略。

Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.