Contribution of Prostaglandin E2-Induced Neuronal Excitation to Drug Resistance in Glioblastoma Countered by a Novel Blood-Brain Barrier Crossing Celecoxib Derivative.

ABSTRACT: Glioblastoma (GBM) is a highly aggressive brain tumor. Its poor prognosis is primarily due to recurrence and resistance to standard therapies, such as temozolomide (TMZ). Emerging evidence suggests that neuronal excitation within the tumor microenvironment contributes to the progression and chemoresistance of GBM. This study identifies prostaglandin E2 (PGE2) as a key regulator of neuronal activity that promotes tumor resistance. It is demonstrated that PGE2 activates neurons via the prostaglandin E1 (EP1) receptor, leading to intracellular calcium influx and phosphorylation of calcium/calmodulin dependent protein kinase II (CaMKII), which enhances synaptic plasticity. Neuronal excitation results in upregulation of synaptic proteins and neurotransmitter alterations, notably increasing glut

SUBMITTER: Shen CJ 

PROVIDER: S-EPMC12520548 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature