Open AccessNeuropilin 1 expression correlates with the Radio‐resistance of human non‐small‐cell lung cancer cells
Author(s) -
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
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12623
Subject(s) - lung cancer , cancer research , biology , cell , neuropilin 1 , medicine , oncology , genetics , vascular endothelial growth factor , vegf receptors
Abstract The purpose of this study was to determine the correlation between over‐expression of the neuropilin 1 ( NRP 1) 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 NRP 1 inhibition on the in vitro growth of NSCLC cells. The Annexin V‐Fluorescein Isothiocyanate (FITC) apoptosis detection assay was performed to analyse the effect of NRP 1 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 VEGFR 2, PI 3K and NF ‐κB. Finally, to examine the effect of sh NRP 1 on proliferation and radio‐sensitivity in 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 (sh NRP 1‐A549) showed a significant reduction in colony‐forming ability and proliferation not only in vitro , but also in vivo . Moreover, sh RNA ‐mediated NRP 1 inhibition also significantly enhanced the radio‐sensitivity of NSCLC cells both in vitro and in vivo . The over‐expression of NRP 1 was correlated with growth, survival and radio‐resistance of NSCLC cells via the VEGF ‐ PI 3K‐ NF ‐κB pathway, and NRP 1 may be a molecular therapeutic target for gene therapy or radio‐sensitization of NSCLC .