2. Academic Validation
  3. Calycosin exerts anti-glioblastoma effects by inhibiting GPX-4 to promote oxidative stress

Calycosin exerts anti-glioblastoma effects by inhibiting GPX-4 to promote oxidative stress

  • Brain Res Bull. 2026 Apr:237:111804. doi: 10.1016/j.brainresbull.2026.111804.
Qin Wei 1,  Kexin Yang 2,  Zhaoyang Liu 3,  Dexuan Kong 2,  Wenbo Pang 2,  Runze Qiu 3,  Hongwei Fan 4,  Yingbin Li 5,  Xiong Zhang 6
Affiliations

Affiliations

  • 1 School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacy, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiang Su 213003, China.
  • 2 Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 3 Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
  • 4 Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
  • 5 Department of Neurosurgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. Electronic address: [email protected].
  • 6 Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. Electronic address: [email protected].
PMID: 41771447 DOI: 10.1016/j.brainresbull.2026.111804
Abstract

Temozolomide (TMZ) is a first-line drug for treating glioblastoma (GBM), but its efficacy has been greatly limited by the development of resistance. Calycosin (CAL), an isoflavone, has demonstrated efficacy in anti-tumor therapy. However, its effect on TMZ-resistant GBM cells remains unclear. This study explored the effects of CAL on the parental and TMZ-resistant GBM cells in vitro and in vivo experiments. The results showed that CAL could significantly inhibit the proliferation, migration, and invasion of both parental and TMZ-resistant GBM cells and promote their Apoptosis, and could exert anti-GBM effects in vivo. Furthermore, by detecting the changes in oxidative stress-related indicators and Glutathione Peroxidase 4 (GPX-4) protein in the resistant cells and tissues after CAL treatment, it was found that the level of Reactive Oxygen Species (ROS) increased, while the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) decreased, and the expression of GPX-4 was lowered. It indicates that the effect of CAL on drug-resistant GBM is related to the inhibition of GPX-4 expression, thereby promoting the occurrence of oxidative stress. In conclusion, CAL has potential clinical application value in the treatment of TMZ-resistant GBM and provides a new approach for the treatment of drug-resistant GBM.

Keywords

Calycosin; Drug resistance; GPX-4; Glioblastoma; Oxidative stress.

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