title: Neuropilin 1 expression correlates with the Radio-resistance of human non-small-cell lung cancer cells.
abstract: 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.
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.|China Institute for Radiation Protection, Taiyuan, China.
authors.forename: Juan Cong
authors.initials: JC
authors.lastname: Dong
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Si Yao
authors.initials: SY
authors.lastname: Zuo
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Hai Qin
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Shi Long
authors.initials: SL
authors.lastname: Sun
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Hai Ling
authors.initials: HL
authors.lastname: Han
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Lin Lin
authors.initials: LL
authors.lastname: Jin
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Li Hong
authors.initials: LH
authors.lastname: Shao
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Ministry of Health Key Laboratory of Radiobiology, Jilin University, Changchun, China.
authors.forename: Shun Zi
authors.initials: SZ
authors.lastname: Jin
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D039942:Neuropilin-1 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011836:Radiation Tolerance / Q000528:radiation effects; D012074:Remission Induction; D014162:Transfection; D014965:X-Rays
chemical_list: D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D039942:Neuropilin-1
keywords: ionizing radiation; neuropilin-1; non-small cell lung cancer; radio-resistance