biostudies-literatureRahman MANorges ForskningsrådKreftforeningen1022191https://www.ebi.ac.uk/biostudies/studies/S-EPMC9814514biostudies-literatureUnknown10<b>Introduction:</b> Glioblastoma (GBM) is invariably resistant to temozolomide (TMZ) chemotherapy. Inhibiting the proteasomal pathway is an emerging strategy to accumulate damaged proteins and inhibit their lysosomal degradation. We hypothesized that pre-treatment of glioblastoma with bortezomib (BTZ) might sensitize glioblastoma to temozolomide by abolishing autophagy survival signals to augment DNA damage and apoptosis. <b>Methods:</b> P3 patient-derived glioblastoma cells, as well as the tumour cell lines U87, HF66, A172, and T98G were investigated for clonogenic survival after single or combined treatment with temozolomide and bortezomib <i>in vitro</i>. We investigated the requirement of functional autophagy machinery by utilizing pharmacological inhibitors or CRISPR-Cas9 knockout (KFrontiers in cell and developmental biologyBortezomib abrogates temozolomide-induced autophagic flux through an ATG5 dependent pathway.PMC9814514230691 2218316786380 171318Birkeland EGoplen DSimonsen ABindesboll CRahman MAEngelsen ASTSarowar SLotsberg MLKnappskog SChekenya MfalseBortezomib abrogates temozolomide-induced autophagic flux through an ATG5 dependent pathway.<b>Introduction:</b> Glioblastoma (GBM) is invariably resistant to temozolomide (TMZ) chemotherapy. Inhibiting the proteasomal pathway is an emerging strategy to accumulate damaged proteins and inhibit their lysosomal degradation. We hypothesized that pre-treatment of glioblastoma with bortezomib (BTZ) might sensitize glioblastoma to temozolomide by abolishing autophagy survival signals to augment DNA damage and apoptosis. <b>Methods:</b> P3 patient-derived glioblastoma cells, as well as the tumour cell lines U87, HF66, A172, and T98G were investigated for clonogenic survival after single or combined treatment with temozolomide and bortezomib <i>in vitro</i>. We investigated the requirement of functional autophagy machinery by utilizing pharmacological inhibitors or CRISPR-Cas9 knockout (K2022-01-01T00:00:00Z20222026-05-28T03:44:00.352Z2025-04-04T20:20:30.633ZS-EPMC98145143661985710.3389/fcell.2022.1022191