Propofol and Glioblastoma Biology: A Narrative Review of Perioperative Clinical Evidence and PI3K/AKT-Wnt-miRNA, GABA-A, and Immune-Checkpoint Pathways.

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor, with a median survival of approximately 15 months despite current multimodal therapies. Recent clinical observations have suggested that the intravenous anesthetic propofol may be used to examine whether anesthetic agents can affect glioblastoma behavior. Several retrospective studies reported that, in surgical settings, propofol-based total intravenous anesthesia (TIVA) is associated with reduced operative time, faster recovery, lower intraoperative blood loss, and decreased postoperative complications such as seizures and cerebral edema, benefits particularly evident in patients with low Karnofsky Performance Scores. However, current clinical evidence remains limited, and the reported effects on survival and recurrence are still inconsistent. Preclinical studies showed that propofol's antitumor potential is mediated through modulation of the PI3K/AKT-Wnt-miRNA axis, reduction of oxidative stress, regulation of immune checkpoint molecules, and restoration of temozolomide sensitivity in resistant cells. However, some reports indicate that propofol may also induce stem-like features via GABA-A receptor activation, underscoring its complex and context-dependent nature. This narrative review summarizes the current molecular and clinical evidence about propofol in GBM. Available laboratory and retrospective clinical studies indicate possible antitumor effects, but the present evidence does not support definitive clinical conclusions. Large prospective and multicenter studies are still needed to clarify the clinical role of propofol in patients with GBM.