Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1.

ABSTRACT:

Introduction

To improve the standard treatment paradigm for glioblastoma (GBM), efforts have been made to explore the efficacy of epigenetic agents as chemosensitizers. Recent data suggest possible synergy between decitabine (DAC), a DNA hypomethylating agent, and temozolomide (TMZ) in GBM, but the mechanism remains unclear. The objective of this study was to determine the effects of DAC on TMZ sensitization in a consecutively derived set of primary GBM cultures, with a focus on mismatch repair (MMR) proteins.

Methods

Half maximal inhibitory concentrations (IC₅₀) of TMZ were calculated in eleven consecutive patient-derived GBM cell lines before and after preconditioning with DAC. MMR protein expression changes were determined by quantitative immunoblots and qPCR a

SUBMITTER: Gallitto M 

PROVIDER: S-EPMC7256087 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature