PARP inhibition restores extrinsic apoptotic sensitivity in glioblastoma.

ABSTRACT:

Background

Resistance to apoptosis is a paramount issue in the treatment of Glioblastoma (GBM). We show that targeting PARP by the small molecule inhibitors, Olaparib (AZD-2281) or PJ34, reduces proliferation and lowers the apoptotic threshold of GBM cells in vitro and in vivo.

Methods

The sensitizing effects of PARP inhibition on TRAIL-mediated apoptosis and potential toxicity were analyzed using viability assays and flow cytometry in established GBM cell lines, low-passage neurospheres and astrocytes in vitro. Molecular analyses included western blots and gene silencing. In vivo, effects on tumor growth were examined in a murine subcutaneous xenograft model.

Results

The combination treatment of PARP inhibitors and TRAIL led to an increased cell death with activation

SUBMITTER: Karpel-Massler G 

PROVIDER: S-EPMC4273972 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature