Lithium enhances the antitumour effect of temozolomide against TP53 wild-type glioblastoma cells via NFAT1/FasL signalling.

ABSTRACT:

Background

We previously showed that activation of the nuclear factor of activated T cells (NFAT)1/Fas ligand (FasL) pathway induces glioma cell death. Lithium (Li) is an inhibitor of glycogen synthase kinase (GSK)-3 that activates NFAT1/FasL signalling. Temozolomide (TMZ) inhibits GSK-3 and activates Fas in tumour protein (TP)53 wild-type (TP53wt) glioma cells. The present study investigated the combinational effects of TMZ and low-dose Li on TP53wt glioma cells.

Methods

The combined effect of TMZ and Li was examined in TP53wt U87 and primary glioma cells and a mouse xenograft model.

Results

Combination with 1.2 mM Li potentiated TMZ-induced cell death in TP53wt glioma cells, as determined by neurosphere formation and apoptosis assays. Temozolomide combined with Li t

SUBMITTER: Han S 

PROVIDER: S-EPMC5482734 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature