Marizomib sensitizes primary glioma cells to apoptosis induced by a latest-generation TRAIL receptor agonist.

ABSTRACT: Due to the absence of curative treatments for glioblastoma (GBM), we assessed the efficacy of single and combination treatments with a translationally relevant 2nd generation TRAIL-receptor agonist (IZI1551) and the blood-brain barrier (BBB) permeant proteasome inhibitor marizomib in a panel of patient-derived glioblastoma cell lines. These cells were cultured using protocols that maintain the characteristics of primary tumor cells. IZI1551+marizomib combination treatments synergistically induced apoptotic cell death in the majority of cases, both in 2D, as well as in 3D spheroid cultures. In contrast, single-drug treatments largely failed to induce noticeable amounts of cell death. Kinetic analyses suggested that time-shifted drug exposure might further increase responsiveness, with mariz

SUBMITTER: Boccellato C 

PROVIDER: S-EPMC8225658 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature