机构：[1]Laboratory of Early Developmental Injuries, West China Institute of Woman and Children's Health, and Department of Pediatrics, West China Second University Hospital, Sichuan University[2]Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education[3]Center for Human Molecular Biology and Genetics, The Key Laboratory for Human Disease Gene Study of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital四川省人民医院[4]Department of Gynecology and Obstetrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital四川省人民医院[5]Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China四川大学华西医院
Nematode anticoagulant protein c2 (NAPc2) is an 85-residue polypeptide originally isolated from the hematophagous hookworm, Ancylostoma caninum. Several studies have shown that rNAPc2 inhibits the growth of primary and metastatic tumors in mice independently of its ability to initiate coagulation. We obtained bioactive recombinant rNAPc2 by splicing of the rNAPc2-intein-CBD fusion proteins expressed in E. coli ER2566. In the in vitro assay, rNAPc2 obviously inhibited the invasive ability of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Furthermore, rNAPc2 suppressed tumor growth in vivo by daily intraperitoneal injection of rNAPc2 in an NSCLC cell xenograft model of nude mice. Respectively, rNAPc2 downregulated the production of urokinase plasminogen activator (uPA) (P<0.05) and suppressed nuclear factor-kappa B (NF-kappa B) activity. We also identified that inhibition of NF-kappa B activity impaired cell invasion and reduced the uPA production in NSCLC cells. Meanwhile, NF-kappa B was found to directly bind to the uPA promoter in vitro. These results demonstrated that rNAPc2 inhibits cell invasion at least in part through the downregulation of the NF-kappa B-dependent metastasis-related gene expression in NSCLC. Our results also suggest that uPA, a known metastasis-promoting gene, is indirectly regulated by rNAPc2 through NF-kappa B activation. These results indicate that rNAPc2 may be a potent agent for the prevention of NSCLC progression.
基金：
National Natural
Science Foundation of China (no. 30800633), the Sichuan
Province Science and Technology Foundation for Youths
(no. 09ZQ026‑034), the Sichuan Province Science and
Technology Foundation (no. 2012SZ0010), and the Program
for Changjiang Scholars and Innovative Research Team in the
University (no. IRT 0935).
第一作者机构：[1]Laboratory of Early Developmental Injuries, West China Institute of Woman and Children's Health, and Department of Pediatrics, West China Second University Hospital, Sichuan University[2]Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education
共同第一作者：
通讯作者：
通讯机构：[3]Center for Human Molecular Biology and Genetics, The Key Laboratory for Human Disease Gene Study of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital[*1]Center for Human Molecular Biology and Genetics, The Key Laboratory for Human Disease Gene Study of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, The Western First Round Road 32, Section 2, Chengdu, Sichuan 610072, P.R. China
推荐引用方式(GB/T 7714)：
Tong Yu,Yue Jun,Mao Meng,et al.Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells[J].ONCOLOGY REPORTS.2015,33(4):1815-1822.doi:10.3892/or.2015.3795.
APA：
Tong, Yu,Yue, Jun,Mao, Meng,Liu, Qingqing,Zhou, Jing&Yang, Jiyun.(2015).Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells.ONCOLOGY REPORTS,33,(4)
MLA：
Tong, Yu,et al."Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells".ONCOLOGY REPORTS 33..4(2015):1815-1822
