niraparib and Carcinoma--Lewis-Lung

Poly-(ADP-Ribose)-Polymerase inhibitors (PARPi) were reported as radiosensitizers in non-small cell lung cancer (NSCLC) with wide-type epidermal growth factor receptor (EGFR), but the effects of radiation combined with PARPi were not investigated in EGFR-mutated NSCLC. Moreover, the underlying mechanisms were not well examined. This study aimed to study the efficacy of radiation combined with niraparib in EGFR-mutated NSCLC and explore their influence on the immune system.. Clone formation and apoptosis assay were conducted to explore the effects of niraparib and radiation. Immunofluorescence was conducted to detect the double-strand DNA breaks. Real-time PCR and immunoblotting were employed to evaluate the activation of STING/TBK1/TRF3 pathway and the expression levels of interferon β, CCL5 and CXCL10. Immunocompetent mice model bearing with subcutaneous Lewis lung cancer was established to confirm the results in vivo.. PARPi not only as a radiosensitizer inhibited EGFR-mutated NSCLC tumor growth, but also cooperated with radiation to promote anti-tumor immune responses.

Topics: Animals; Carcinoma, Lewis Lung; Carcinoma, Non-Small-Cell Lung; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Chemokine CCL5; Chemokine CXCL10; Chemoradiotherapy; DNA Breaks, Double-Stranded; Female; Fluorescent Antibody Technique; Genes, erbB-1; Humans; Immune System; Immunocompetence; Indazoles; Interferon Regulatory Factor-3; Interferon-beta; Lung Neoplasms; Lymphocytes, Tumor-Infiltrating; Membrane Proteins; Mice; Mice, Inbred C57BL; Mutation; Nuclear Proteins; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Protein Serine-Threonine Kinases; Radiation Tolerance; Radiation-Sensitizing Agents; Real-Time Polymerase Chain Reaction; TATA Box Binding Protein-Like Proteins; Tumor Stem Cell Assay