RTA-408 Enhances Radiosensitivity and Inhibited Tumor Progression via JNK Pathway in Glioblastoma

Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis owing to its high invasiveness and resistance to therapy. RTA-408, a synthetic triterpenoid and nuclear factor erythroid 2-related factor 2 activator, exhibits anti-inflammatory and anti-cancer properties; however, its effects on GBM remain unclear. This study investigated the therapeutic potential of RTA-408 in GBM, focusing on its role in the activation of the JNK pathway. GBM8401 and A172 cells were treated with RTA-408, and cell viability, apoptosis, migration, and radiosensitivity were assessed. Western blot analysis was used to evaluate the epithelial-mesenchymal transition markers, cyclin D1, and JNK signaling. Intracranial xenograft models were used to assess tumor growth suppression by RTA-408 alone or in combination with radiotherapy. RTA-408 significantly reduced cell viability, induced apoptosis, and inhibited the migration of GBM cells, correlating with the activation of the JNK pathway. JNK inhibition reversed these effects, confirming its role in RTA-408-mediated tumor suppression. RTA-408 also enhanced radiosensitivity and reduced clonogenic survival. RTA-408 suppressed GBM tumor growth in vivo, with the greatest effect observed in combination with radiotherapy. RTA-408 exerts antitumour and radiosensitizing effects via activation of the JNK pathway and inhibits GBM progression. These findings highlight its potential as a novel therapeutic strategy for the treatment of GBM.