2. Academic Validation
  3. Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma

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

  • Cell Death Dis. 2023 Mar 25;14(3):211. doi: 10.1038/s41419-023-05738-8.
Jiayang Cai # 1 2,  Zhang Ye # 1 2,  Yuanyuan Hu # 3,  Liguo Ye 1 2,  Lun Gao 1 2,  Yixuan Wang 1 2,  Qian Sun 1 2,  Shiao Tong 1 2,  Shenqi Zhang 1 2,  Liquan Wu 1 2,  Ji'an Yang 4 5,  Qianxue Chen 6 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, China.
  • 2 Central Laboratory, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, China.
  • 3 Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.
  • 4 Department of Neurosurgery, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, China. jayang@whu.edu.cn.
  • 5 Central Laboratory, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, China. jayang@whu.edu.cn.
  • 6 Department of Neurosurgery, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, China. chenqx666@whu.edu.cn.
  • 7 Central Laboratory, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, China. chenqx666@whu.edu.cn.
  • # Contributed equally.
PMID: 36966152 DOI: 10.1038/s41419-023-05738-8
Abstract

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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