Neuropilin 1 expression correlates with the Radio-resistance of human non-small-cell lung cancer cells

作者：Dong, Juan Cong; Gao, Hui; Zuo, Si Yao; Zhang, Hai Qin; Zhao, Gang; Sun, Shi Long; Han, Hai Ling; Jin, Lin Lin; Shao, Li Hong; Wei, Wei; Jin, Shun Zi^*

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2015, 19(9): 2286-2295.

DOI：10.1111/jcmm.12623

• ionizing radiation
• neuropilin-1
• non-small cell lung cancer
• radio-resistance

The 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 of NRP1 inhibition on the invitro growth of NSCLC cells. The Annexin V-Fluorescein Isothiocyanate (FITC) apoptosis detection assay was performed to analyse the effect of NRP1 enhancement on apoptosis of NSCLC cells. 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 of VEGFR2, PI3K and NF-B. Finally, to examine the effect of shNRP1 on proliferation and radio-sensitivity invivo, 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 only invitro, but also invivo. Moreover, shRNA-mediated NRP1 inhibition also significantly enhanced the radio-sensitivity of NSCLC cells both invitro and invivo. The over-expression of NRP1 was correlated with growth, survival and radio-resistance of NSCLC cells via the VEGF-PI3K- NF-B pathway, and NRP1 may be a molecular therapeutic target for gene therapy or radio-sensitization of NSCLC.

• 出版日期2015-9
• 单位中国辐射防护研究院; 吉林大学