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

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.