ZSTK474 Sensitizes Glioblastoma to Temozolomide by Blocking Homologous Recombination Repair.

ABSTRACT: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Temozolomide (TMZ) is used as the standard chemotherapeutic agent for GBM but with limited success, and treatment failure is mainly due to tumor resistance. One of the leading causes of TMZ resistance is the upregulation of the DNA repair mechanism. Therefore, targeting the DNA damage response (DDR) is proposed to be an effective strategy to sensitize tumor cells to TMZ. In the present study, we demonstrated that the combined use of the PI3K inhibitor ZSTK474 and TMZ showed synergetic anticancer effects on human GBM cells in vitro and in vivo. The combination treatment led to significantly increased cell apoptosis and DNA double strand breaks (DSBs). In addition, a mechanistic study indicated that TMZ enhanced t

SUBMITTER: Jiao W 

PROVIDER: S-EPMC9300311 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature