Selinexor reduces the expression of DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents.

ABSTRACT:

Introduction

The goal of this study was to examine the effects of selinexor, an inhibitor of exportin-1 mediated nuclear export, on DNA damage repair and to evaluate the cytotoxic effects of selinexor in combination with DNA damaging agents (DDAs) in cancer cells.

Results

Selinexor reduced the expression of DNA damage repair (DDR) proteins. This did not induce significant DNA damage in tested cell lines. Inhibition of DDR protein expression resulted in enhanced cancer cell death when cells were pretreated with DDAs. In contrast, enhanced cell death was not detected in cells that were pretreated with selinexor then with DDAs. In vivo, single-agent selinexor, docetaxel, or cisplatin treatment resulted in 66.7%, 51.5%, and 26.6% tumor growth inhibition (TGI), respectivel

SUBMITTER: Kashyap T 

PROVIDER: S-EPMC6089403 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature