Iranian Journal of Basic Medical Sciences، جلد ۲۴، شماره ۴، صفحات ۴۹۹-۵۰۵

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عنوان انگلیسی Pathogenic role of the SP/ NK1R system in GBM cells through inhibiting the thioredoxin system
چکیده انگلیسی مقاله Objective(s): Glioblastoma multiforme (GBM), a highly aggressive Grade IV brain tumor, is a significant public health issue due to its poor prognosis and incurability. Neuropeptide substance P (SP) plays a critical role in GBM tumor growth and development via activation of neurokinin‐1receptor (NK1R). Moreover, SP is a pro-oxidant factor contributing to oxidative stress in various cell types. However, the link between SP and oxidative stress in cancer cells is not fully investigated. Here, we aimed to identify the effects of SP and NK1R antagonist, aprepitant, on the redox status of GBM cells.Materials and Methods: Resazurin assay was employed to determine the effect of aprepitant on viability of U87 glioblastoma cells. 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) assay was employed to measure the levels of intracellular reactive oxygen species (ROS). A quantitative real-time polymerase chain reaction was applied to measure the expression of proteins of the thioredoxin system. Commercial kits (ZellBio GmbH) were also used to measure the enzymatic activity of these proteins.Results: We found that SP increased ROS level in U87 GBM cells, and aprepitant significantly reduced this effect. Furthermore, we found that SP could also affect the thioredoxin system, a central antioxidant enzyme defense system. SP reduced both expression and enzymatic activity of the thioredoxin system’s proteins, Trx and thioredoxin reductase (TrxR) and these effects were significantly reduced by aprepitant. Conclusion: Our results indicated that SP activation of NK1R represented a link between oxidative stress and GBM and highlighted the need for further validations in future studies.
کلیدواژه‌های انگلیسی مقاله Glioblastoma multiforme, Neurokinin 1 receptor, Oxidative stress, Substance P, Thioredoxin

نویسندگان مقاله | Fatemeh Ghahremani
Department of Biology, Faculty of Science, Hakim Sabzevari University, Sabzevar, Iran


| Reihaneh Sabbaghzade
Department of Biology, Faculty of Science, Hakim Sabzevari University, Sabzevar, Iran


| Safieh Ebrahimi
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


| Hosein Javid
Medical Laboratory Sciences Department, Varastegan Institute for Medical Sciences, Mashhad, Iran


| Javad Ghahremani
Department of Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


| Seyed Isaac Hashemy
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran|Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran



نشانی اینترنتی https://ijbms.mums.ac.ir/article_17739.html
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