title: [Inhibitory effect of nimesulide and oxaliplatin on tumor growth and lymphatic metastasis of transplanted human lung cancer in nude mice].
abstract: OBJECTIVE
  This study was designed to evaluate the inhibitory effect of nimesulide in combination with oxaliplatin on tumor growth, expression of COX-2, VEGF-C, VEGFR-3, survivin and β-catenin, and lymphatic metastasis in lung cancer xenograft in nude mice, and to discuss the possible synergistic effect of nimesulide in combination with oxaliplatin.
  
  
  METHODS
  Human lung cancer A549 cells were injected into BALB/c nude mice subcutaneously. Thirty-three healthy male nude mice were randomly divided into 4 groups: the control group, nimesulide group, oxaliplatin group and nimesulide combined with oxaliplatin group. Transplanted tumor tissues were collected and the expressions of COX-2, VEGF-C, VEGFR-3, survivin, β-catenin protein were detected by immunohistochemistry, and RT-PCR assay was used to assess the expression of tumor COX-2, VEGF-C, VEGFR-3, survivin and β-catenin mRNA. SPSS 16.0 was used for statistical analysis. Data were present as (x(-) ± s), and the means were compared by analysis of variance test.
  
  
  RESULTS
  Tumor inhibition rates of the nimesulide group, oxaliplatin group and nimesulide + oxaliplatin group were 39.73%, 48.04% and 65.94%, respectively. Immunohistochemical and RT-PCR analysis showed that compared with the control group, the expression levels of COX-2, VEGF-C, VEGFR-3, survivin and β-catenin of the nimesulide group were significantly reduced (all P < 0.05). Compared with the control group, statistical analysis of variance showed that the expression levels of COX-2, VEGF-C and VEGFR-3 of the oxaliplatin group were significantly increased (P < 0.05), the expression levels of survivin and β-catenin protein and mRNA of the oxaliplatin group were significantly reduced (P < 0.05). Compared with the control group, the expression levels of COX-2, VEGF-C, VEGFR-3, survivin and β-catenin of the nimesulide + oxaliplatin group were significantly reduced (all P < 0.05).
  
  
  CONCLUSIONS
  Both nimesulide alone or in combination with oxaliplatin can significantly inhibit the growth of lung cancer xenografts in nude mice and the expression levels of COX-2, VEGF-C, VEGFR-3, survivin and β-catenin. Oxaliplatin can significantly inhibit the growth of lung cancer xenografts in nude mice, and the expression of survivin and β-catenin. Nimesulide in combination with oxaliplatin enhances the antitumor effect of oxaliplatin.
authors.affiliation: Department of Respiratory Diseases, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Dong-chang
authors.initials: DC
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013449:Sulfonamides / Q000494:pharmacology*; D000077022:Survivin; D047368:Tumor Burden / Q000187:drug effects*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; C495270:CTNNB1 protein, human; D016861:Cyclooxygenase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D013449:Sulfonamides; D000077022:Survivin; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D051176:beta Catenin; D000077150:Oxaliplatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3; C012655:nimesulide