1. Academic Validation
  2. Remdesivir inhibits the progression of glioblastoma by enhancing endoplasmic reticulum stress

Remdesivir inhibits the progression of glioblastoma by enhancing endoplasmic reticulum stress

  • Biomed Pharmacother. 2022 Nov 22;157:114037. doi: 10.1016/j.biopha.2022.114037.
Yujia Chen 1 Yuduo Guo 1 Shenglun Li 1 Jiacheng Xu 1 Weihai Ning 1 Chao Zhao 1 Jun Wang 1 Yanming Qu 1 Mingshan Zhang 1 Wanlu Zhou 2 Qinghua Cui 3 Hongwei Zhang 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
  • 2 Co., Ltd of JeaMoon Technology, 6Rd Middle Zuojiazhuang, Beijing 100028, China.
  • 3 Co., Ltd of JeaMoon Technology, 6Rd Middle Zuojiazhuang, Beijing 100028, China. Electronic address: cuiqinghua@hsc.pku.edu.cn.
  • 4 Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China. Electronic address: zhanghongwei@ccmu.edu.cn.
Abstract

Glioblastoma (GBM) is one of the most aggressive primary malignant brain tumors. The major challenge is the lack of effective therapeutic drugs due to the blood-brain barrier (BBB) and tumor heterogeneity. Remdesivir (RDV), a new member of the nucleotide analog family, has previously been shown to have excellent Antiviral effects and BBB penetration, and was predicted here to have anti-GBM effects. In vitro experiments, RDV significantly inhibited the growth of GBM cells, with IC50 values markedly lower than those of normal cell lines or the same cell lines treated with temozolomide. Moreover, in multiple mouse models, RDV not only distinctly inhibited the progression and improved the prognosis of GBM but also exhibited a promising biosafety profile, as manifested by the lack of significant body weight loss, liver or kidney dysfunction or organ structural damage after administration. Furthermore, we investigated the anti-GBM mechanism by RNA-seq and identified that RDV might induce Apoptosis of GBM cells by enhancing endoplasmic reticulum (ER) stress and activating the PERK-mediated unfolded protein response. In conclusion, our results indicated that RDV might serve as a novel agent for GBM treatment by increasing ER stress and inducing Apoptosis in GBM cells.

Keywords

Apoptosis; Endoplasmic reticulum stress; Glioblastoma; PERK-mediated unfolded protein response; Remdesivir.

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