title: [Inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung cancer xenografts in nude mice].
abstract: OBJECTIVE
  To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms.
  
  
  METHODS
  Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty-eight healthy male nude mice were randomly divided into 4 groups: the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E-cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E-cadherin mRNA were detected by real-time PCR.
  
  
  RESULTS
  The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm(3)] and combination group [(507.74±77.50) mm(3)] were significantly lower than that of the control group (1355.33±189.04) mm(3) (P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level; 0.54±0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E-cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group (253.78±38.87, 308.94±24.67 vs. 213.66±30.31 for protein expression level; 2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both). There was a significant negative correlation between ezrin protein and E-cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E-cadherin mRNA (r=-0.977, P<0.01).
  
  
  CONCLUSIONS
  Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non-small cell lung cancer xenografts and lymph node metastasis via down-regulated ezrin and upregulated E-cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.
authors.affiliation: Department of Respiratory Diseases, the Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: D C
authors.initials: DC
authors.lastname: Wang
authors.affiliation: Department of Respiratory Diseases, the Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: L C
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, the First Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: L J
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Respiratory Diseases, the Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Respiratory Diseases, the Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Diseases, the Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Z F
authors.initials: ZF
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Diseases, the Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003503:Cyclobutanes / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013440:Sulfides / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects; D000099149:Ezrin
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D003503:Cyclobutanes; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D011758:Pyrroles; D012333:RNA, Messenger; D013440:Sulfides; D000099149:Ezrin; C488833:Imrecoxib; C066228:lobaplatin