Topoisomerase I Inhibition Radiosensitizing Hepatocellular Carcinoma by RNF144A-mediated DNA-PKcs Ubiquitination and Natural Killer Cell Cytotoxicity.

ABSTRACT:

Background and aims

Topoisomerase I (TOP1) participates the repair of DNA double-strand breaks (DSBs) upon radiation therapy (RT). RNF144A mediates ubiquitination of catalytic subunit of DNA protein kinase (DNA-PKcs), a critical factor in DSB repair. This study aimed to investigate the natural killer (NK) cell-mediated radiosensitization with TOP1 inhibition and the mechanism by DNA-PKcs/RNF144A.

Methods

In vitro synergism with TOP1i or cocultured NK cells and RT were evaluated in human hepatocellular carcinoma (HCC) cell lines (Huh7/PLC5) by clonogenic survivals. Orthotopic xenografts were treated with Lipotecan and/or RT. Protein expression was analyzed by western blotting, immunoprecipitation, subcellular fractionation, and confocal microscopy.

Results

Lipot

SUBMITTER: Tsai CL 

PROVIDER: S-EPMC10037509 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature