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Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma

Glioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, the median survival of GBM patients is unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including...

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Autores principales: Cai, Jiayang, Ye, Zhang, Hu, Yuanyuan, Ye, Liguo, Gao, Lun, Wang, Yixuan, sun, Qian, Tong, Shiao, Zhang, Shenqi, Wu, Liquan, Yang, Ji’an, Chen, Qianxue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039896/
https://www.ncbi.nlm.nih.gov/pubmed/36966152
http://dx.doi.org/10.1038/s41419-023-05738-8
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author Cai, Jiayang
Ye, Zhang
Hu, Yuanyuan
Ye, Liguo
Gao, Lun
Wang, Yixuan
sun, Qian
Tong, Shiao
Zhang, Shenqi
Wu, Liquan
Yang, Ji’an
Chen, Qianxue
author_facet Cai, Jiayang
Ye, Zhang
Hu, Yuanyuan
Ye, Liguo
Gao, Lun
Wang, Yixuan
sun, Qian
Tong, Shiao
Zhang, Shenqi
Wu, Liquan
Yang, Ji’an
Chen, Qianxue
author_sort Cai, Jiayang
collection PubMed
description Glioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, the median survival of GBM patients is unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including new drugs and drug delivery approaches. Ferroptosis, a kind of regulated cell death (RCD), has been shown to be dysregulated in various tumors, including GBM. Fatostatin, a specific inhibitor of sterol regulatory element binding proteins (SREBPs), is involved in lipid and cholesterol synthesis and has antitumor effects in a variety of tumors. However, the effect of fatostatin has not been explored in the field of ferroptosis or GBM. In our study, through transcriptome sequencing, in vivo experiments, and in vitro experiments, we found that fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. We also designed a p28-functionalized PLGA nanoparticle loaded with fatostatin, which could better cross the blood-brain barrier (BBB) and be targeted to GBM. Our research identified the unprecedented effects of fatostatin in GBM and presented a novel drug-targeted delivery vehicle capable of penetrating the BBB in GBM.
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spelling pubmed-100398962023-03-27 Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma Cai, Jiayang Ye, Zhang Hu, Yuanyuan Ye, Liguo Gao, Lun Wang, Yixuan sun, Qian Tong, Shiao Zhang, Shenqi Wu, Liquan Yang, Ji’an Chen, Qianxue Cell Death Dis Article Glioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, the median survival of GBM patients is unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including new drugs and drug delivery approaches. Ferroptosis, a kind of regulated cell death (RCD), has been shown to be dysregulated in various tumors, including GBM. Fatostatin, a specific inhibitor of sterol regulatory element binding proteins (SREBPs), is involved in lipid and cholesterol synthesis and has antitumor effects in a variety of tumors. However, the effect of fatostatin has not been explored in the field of ferroptosis or GBM. In our study, through transcriptome sequencing, in vivo experiments, and in vitro experiments, we found that fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. We also designed a p28-functionalized PLGA nanoparticle loaded with fatostatin, which could better cross the blood-brain barrier (BBB) and be targeted to GBM. Our research identified the unprecedented effects of fatostatin in GBM and presented a novel drug-targeted delivery vehicle capable of penetrating the BBB in GBM. Nature Publishing Group UK 2023-03-25 /pmc/articles/PMC10039896/ /pubmed/36966152 http://dx.doi.org/10.1038/s41419-023-05738-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Cai, Jiayang
Ye, Zhang
Hu, Yuanyuan
Ye, Liguo
Gao, Lun
Wang, Yixuan
sun, Qian
Tong, Shiao
Zhang, Shenqi
Wu, Liquan
Yang, Ji’an
Chen, Qianxue
Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma
title Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma
title_full Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma
title_fullStr Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma
title_full_unstemmed Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma
title_short Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma
title_sort fatostatin induces ferroptosis through inhibition of the akt/mtorc1/gpx4 signaling pathway in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039896/
https://www.ncbi.nlm.nih.gov/pubmed/36966152
http://dx.doi.org/10.1038/s41419-023-05738-8
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