Discordant in vitro and in vivo chemopotentiating effects of the PARP inhibitor veliparib in temozolomide-sensitive versus -resistant glioblastoma multiforme xenografts.

ABSTRACT:

Purpose

Effective sensitizing strategies potentially can extend the benefit of temozolomide (TMZ) therapy in patients with glioblastoma (GBM). We previously demonstrated that robust TMZ-sensitizing effects of the [poly (ADP-ribose) polymerase] (PARP) inhibitor veliparib (ABT-888) are restricted to TMZ-sensitive GBM xenografts. The focus of this study is to provide an understanding for the differential sensitization in paired TMZ-sensitive and -resistant GBM models.

Experimental design

The impact of veliparib on TMZ-induced cytotoxicity and DNA damage was evaluated in vitro and in vivo in models of acquired TMZ resistance (GBM12TMZ-mgmt(High), GBM12TMZ-mgmt(Low), and U251TMZ), inherent TMZ resistance (T98G), and TMZ-sensitive (U251 and GBM12). In vivo drug efficacy, pharmacok

SUBMITTER: Gupta SK 

PROVIDER: S-EPMC4111895 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature