2. Academic Validation
  3. Lower dose of metformin combined with artesunate induced autophagy-dependent apoptosis of glioblastoma by activating ROS-AMPK-mTOR axis

Lower dose of metformin combined with artesunate induced autophagy-dependent apoptosis of glioblastoma by activating ROS-AMPK-mTOR axis

  • Exp Cell Res. 2023 Jul 1;113691. doi: 10.1016/j.yexcr.2023.113691.
Wencong Ding 1,  Lingxiao Liao 2,  Jia Liu 3,  Jiaxing Zhao 1,  Qiongyan Tang 4,  Yongshi Liao 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China.
  • 2 Department of Pharmacy, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China.
  • 3 Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China.
  • 4 Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: 865651041@qq.com.
  • 5 Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China. Electronic address: liaoys66@163.com.
PMID: 37399981 DOI: 10.1016/j.yexcr.2023.113691
Abstract

Glioblastoma multiform (GBM), one of the most common, aggressive primary brain tumours, demonstrates resistance to radiotherapy and chemotherapy after surgical resection and treatment failure. Metformin (MET) has been shown to suppress the proliferative capacity and invasion ability of GBM cells by activating AMPK and inhibiting mTOR, but the effective dose exceeded the maximum tolerated dose. Artesunate (ART) can exert certain anti-tumour effects by activating the AMPK-mTOR axis and inducing Autophagy in tumour cells. Therefore, this study investigated the effects of MET combined with ART combination therapy on Autophagy and Apoptosis in GBM cells. MET combined with ART treatment effectively suppressed the viability, mono-cloning ability, migration and invasion capacities, as well as metastatic ability of GBM cells. The underlying mechanism involved modulation of the ROS-AMPK-mTOR axis, which was confirmed using 3-methyladenine and rapamycin to inhibit or promote the effects of MET combined with ART, respectively. The study findings suggest that MET used in combination with ART can induce autophagy-dependent Apoptosis in GBM cells by activating the ROS-AMPK-mTOR pathway, providing a potential new treatment for GBM.

Keywords

Artesunate; Autophagy; Autophagy-dependent apoptosis; Glioblastoma; Metformin.

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