title: Lentivirus-mediated shRNA interference targeting cyclooxygenase-2 inhibits growth of human non-small cell lung cancer.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2), one isoform of cyclooxygenase proinflammatory enzymes, plays an important role in tumor development and progression. Researches of human cancers have revealed high expression levels of COX-2 in a variety of cancers including lung cancer. The mechanism of COX-2 in the pathogenesis of non-small cell lung cancer (NSCLC) cells is not well understood.
  
  
  METHODS
  We constructed a lentivirus vector mediated RNA interference (RNAi) targeting COX-2 for the treatment of human NSCLC cells. RNAi technology was used to knockdown the expression of COX-2 in NSCLC cell lines. The efficiency and specificity was validated by quantitative real-time PCR and western blotting. The cell growth and cell cycle were determined by MTT and flow cytometry assay, respectively. Cell cycle-regulated gene expression, including cyclin D1, p21 and survivin, whose expression was modulated by COX-2, was also examined.
  
  
  RESULTS
  LV-COX-2-silencing (si)RNA lentivirus vector was effective and its inhibitory effects on COX-2 mRNA and protein expression was efficient and specific. Gene knockdown of COX-2 by LV-COX-2-siRNA significantly inhibited the growth and induced cell cycle arrest of NSCLC cell lines. In addition, silence of COX-2 mediated by LV-COX-2-siRNA modulated the expression of cell cycle-regulated gene, upregulating p21 and downregulating cyclin D1 and survivin.
  
  
  CONCLUSIONS
  Our findings imply that COX-2 and its signaling pathway may provide a novel therapeutic target for the treatment of NSCLC.
authors.affiliation: Cadre Wards, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Tianrong
authors.initials: T
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D015398:Signal Transduction; D000077022:Survivin; D014162:Transfection
chemical_list: C107489:BIRC5 protein, human; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human