AbstractThe purpose of this study was to determine the correlation between over‐expression of the neuropilin 1 (NRP1) gene and growth, survival, and radio‐sensitivity of non‐small cell lung carcinoma (NSCLC) cells. 3‐[4,5‐dimethylthylthiazol‐2‐yl]‐2,5 diphenyltetrazolium broide (MTT) and colony assays were then performed to determine the effect ofNRP1 inhibition on thein vitrogrowth ofNSCLCcells. The Annexin V‐Fluorescein Isothiocyanate (FITC) apoptosis detection assay was performed to analyse the effect ofNRP1 enhancement on apoptosis ofNSCLCcells. Transwell invasion and migration assays were employed to examine the metastatic ability of A549 cells post X‐ray irradiation. In addition, Western blot assays were carried out to detect the protein level ofVEGFR2,PI3K andNF‐κB. Finally, to examine the effect of shNRP1 on proliferation and radio‐sensitivityin vivo, a subcutaneous tumour formation assay in nude mice was performed. Microvessel density in tumour tissues was assessed by immunohistochemistry. The stable transfected cell line (shNRP1‐A549) showed a significant reduction in colony‐forming ability and proliferation not onlyin vitro, but alsoin vivo. Moreover, shRNA‐mediatedNRP1 inhibition also significantly enhanced the radio‐sensitivity ofNSCLCcells bothin vitroandin vivo. The over‐expression ofNRP1 was correlated with growth, survival and radio‐resistance ofNSCLCcellsviatheVEGF‐PI3K‐NF‐κB pathway, andNRP1 may be a molecular therapeutic target for gene therapy or radio‐sensitization ofNSCLC.