DNA-PK Inhibition by NU7441 Enhances Chemosensitivity to Topoisomerase Inhibitor in Non-Small Cell Lung Carcinoma Cells by Blocking DNA Damage Repair.

ABSTRACT:

Background

DNA double-strand breaks (DSBs) are the most cytotoxic form of DNA damage and are induced by ionizing radiation and specific chemotherapeutic agents, such as topoisomerase inhibitors. Cancer cells acquire resistance to such therapies by repairing DNA DSBs. A major pathway for the repair of DNA DSBs is non-homologous end-joining (NHEJ), which requires DNA-dependent protein kinase (DNA-PK) activity. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-PK on the chemosensitization of non-small cell lung carcinoma (NSCLC) A549 cells.

Methods

The combined effects of chemotherapeutic agents and NU7441 were evaluated by isobologram analysis using Cell Counting Kit-8. DNA DSBs were assessed by immunofluor

SUBMITTER: Yanai M 

PROVIDER: S-EPMC5355839 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature