Neuropilin 1 expression correlates with the Radio-resistance of human non-small-cell lung cancer cells
| Autor: | Lin Lin Jin, Hui Gao, Hai Ling Han, Shun Zi Jin, Shi Long Sun, Si Yao Zuo, Gang Zhao, Juan Cong Dong, Wei Wei, Hai Qin Zhang, Li Hong Shao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Lung Neoplasms
Cell Survival Cell Biology Transfection Radiation Tolerance Mice Annexin Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor Neuropilin 1 medicine Animals Humans Neoplasm Invasiveness RNA Small Interfering PI3K/AKT/mTOR pathway non-small cell lung cancer A549 cell Neovascularization Pathologic X-Rays Remission Induction Cell Biology Original Articles Molecular biology Neuropilin-1 respiratory tract diseases Neoplasm Proteins medicine.anatomical_structure Apoptosis Cell culture radio-resistance Gene Knockdown Techniques Molecular Medicine ionizing radiation |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | 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 in vitro 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-κB. Finally, to examine the effect of shNRP1 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 (shNRP1-A549) showed a significant reduction in colony-forming ability and proliferation not only in vitro, but also in vivo. Moreover, shRNA-mediated NRP1 inhibition also significantly enhanced the radio-sensitivity of NSCLC cells both in vitro and in vivo. The over-expression of NRP1 was correlated with growth, survival and radio-resistance of NSCLC cells via the VEGF-PI3K- NF-κB pathway, and NRP1 may be a molecular therapeutic target for gene therapy or radio-sensitization of NSCLC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text