Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Biomed Res Int. 2022 Mar 3;2022:8540403. doi: 10.1155/2022/8540403. eCollection 2022.
Although there is no doubt regarding the involvement of oxidative stress in the development of glioblastoma, many questions remained unanswered about signaling cascades that regulate the redox status. Given the importance of the substance P (SP)/neurokinin 1 receptor (NK1R) system in different cancers, it was of particular interest to evaluate whether the stimulation of this cascade in glioblastoma-derived U87 cells is associated with the induction of oxidative stress. Our results showed that SP-mediated activation of NK1R not only increased the intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS) but also reduced the concentration of thiol in U87 cells. We also found that upon SP addition, there was a significant reduction in the cells' total antioxidant capacity (TAC), revealing that the SP/NK1R axis may be involved in the regulation of oxidative stress in glioblastoma cells. The significant role of SP/NK1R in triggering oxidative stress in glioblastoma has become more evident when we found that the abrogation of the axis using aprepitant reduced cell survival, probably through exerting antioxidant effects. The results showed that both MDA and ROS concentrations were significantly reduced in the presence of aprepitant, and the number of antioxidant components of the redox system increased. Overall, these findings suggest that aprepitant might exert its anticancer effect on U87 cells through shifting the balance of oxidant and antioxidant components of the redox system.
尽管氧化应激在胶质母细胞瘤的发展中起作用已毋庸置疑，但调控氧化还原状态的信号级联仍存在许多未解之谜。鉴于 P 物质（SP）/神经激肽 1 受体（NK1R）系统在不同癌症中的重要性，评估 SP 刺激是否与胶质母细胞瘤衍生的 U87 细胞中的氧化应激诱导有关，这是特别有趣的。我们的结果表明，SP 介导的 NK1R 激活不仅增加了丙二醛（MDA）和活性氧（ROS）的细胞内水平，而且降低了 U87 细胞中的硫醇浓度。我们还发现，SP 加入后，细胞总抗氧化能力（TAC）显著降低，表明 SP/NK1R 轴可能参与调节胶质母细胞瘤细胞的氧化应激。当我们发现使用 aprepitant 阻断该轴可减少细胞存活时，SP/NK1R 在触发胶质母细胞瘤氧化应激中的重要作用变得更加明显，这可能是通过发挥抗氧化作用。结果表明，在 aprepitant 存在的情况下，MDA 和 ROS 浓度均显著降低，并且氧化还原系统的抗氧化成分数量增加。总体而言，这些发现表明 aprepitant 可能通过改变氧化还原系统的氧化剂和抗氧化剂成分的平衡，对 U87 细胞发挥抗癌作用。
