<i>LINCS</i> gene expression signature analysis revealed bosutinib as a radiosensitizer of breast cancer cells by targeting eIF4G1

Radioresistance is the predominant cause for radiotherapy failure and disease progression, resulting in increased breast cancer‑associated mortality. Using gene expression signature analysis of Library Integrated Network‑Based Cellular Signatures (LINCS) Gene Expression Omnibus (GEO), aim present study was to systematically identify potential candidate radiosensitizers from known drugs. The similarity integrated signatures between irradiated eukaryotic translation initiation factor 4 γ 1 (eIF4G1)‑silenced cancer cells drugs measured using enrichment scores (ES). Drugs with positive ES were selected as radiosensitizers. radiosensitizing effects analyzed cell lines (MCF‑7, MX‑1 MDA‑MB‑231) CCK‑8 colony formation assays following exposure ionizing radiation. Cell apoptosis flow cytometry. levels eIF4G1 DNA damage response (DDR) proteins by western blotting. Bosutinib identified a promising radiosensitizer, its administration markedly reduced dosage required both drug radiation, which may be associated fewer treatment‑associated adverse reactions. Moreover, combined treatment radiation bosutinib significantly killing all three lines, compared or alone. Among most sensitive bosutinib. downregulated dose‑dependent manner also DDR (including ATM, XRCC4, ATRIP, GADD45A). key target that regulate induced Thus, serve radiosensitizer therapy.