XPO1-inhibitor Selinexor induces MGMT expression by activating PKA-CREB signaling in <i>IDH</i> wildtype glioblastoma.

ABSTRACT:

Purpose

The temozolomide (TMZ) resistance mechanisms in MGMT-promoter methylated IDH wildtype glioblastoma (GBM) tumors are poorly known. This study aimed to identify potential modulators of TMZ resistance in methylated GBM cells.

Methods

A genome-wide shRNA library screen was conducted to identify genes modulating resistance in a TMZ-resistant model of MGMT-methylated U251 GBM cells. The Incucyte Device was used for live cell growth monitoring, and DNA damage was assessed by foci staining.

Results

Exportin (XPO1) was among the identified candidate TMZ-resistant genes, and the XPO1 inhibitor Selinexor was selected for further investigations. The MGMT-unmethylated GBM6 cells were sensitive to Selinexor alone, without additional sensitization when c

SUBMITTER: Mapunda JA 

PROVIDER: S-EPMC12500652 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature