title: [A study on the effects of indomethacin and oxaliplatin on lymphangiogenesis in a nude mice model of transplantation with A549 human lung cancer].
abstract: OBJECTIVE
  To investigate the antitumor lymphangiogenesis activity and the synergistic effect of indomethacin and oxaliplatin in a transplantation tumor model of human lung cancer in nude mice.
  
  
  METHODS
  Human lung cancer A549 cells were injected subcutaneously into BALB/c nude mice. The mice were randomly divided into 4 groups: the control group, the indomethacin group, the oxaliplatin group, and the indomethacin combined with oxaliplatin group. The tumor volume was measured in a 7 day interval, and the mice were sacrificed after 42 days. The tumor tissues were collected and prepared for detection by immunohistochemistry of expressions of VEGF-C, Survivin, β-catenin and intratumoral microlymphatic density(MLD). Real-time fluorescence quantitative RT-PCR was performed for detecting the expression of VEGF-C and Survivin mRNA. SPSS version 16.0 was used for statistical analysis. Data were present as (x(-) ± s), and means were compared with analysis of variance. The correlation of 2 variables was analyzed by liner correlation analysis.
  
  
  RESULTS
  The tumor volumes in the indomethacin group, oxaliplatin group, and indomethacin plus oxaliplatin group [(1322 ± 327) mm(3), (962 ± 221) mm(3), (611 ± 161) mm(3)] decreased significantly as compared with that of the control group [(1664 ± 318) mm(3), F = 23.331, P < 0.01]. Compared with the control group, the expression levels of VEGF-C, Survivin, β-catenin and MLD protein in the indomethacin group, and indomethacin plus oxaliplatin group were significantly reduced (P < 0.05). Immunohistochemical studies showed an increase in the expression of VEGF-C in the oxaliplatin group (20 825 ± 2067) as compared to the control group (16 075 ± 875, F = 97.24, P < 0.05), but no significant differences in β-catenin and MLD (17 396 ± 1693, 9666 ± 978) as compared with the control group (9824 ± 1181, 17 588 ± 1698)respectively, P > 0.05. VEGF-C and Survivin proteins were positively correlated with MLD respectively (t = 0.737, 0.662, respectively P < 0.01), and β-catenin protein was positively correlated with Survivin protein (r = 0.582, P < 0.01). VEGF-CmRNA was positively correlated with its protein (r = 0.873, P < 0.01).
  
  
  CONCLUSIONS
  The combined use of indomethacin and oxaliplatin promoted antitumor lymphangiogenesis activity, possible by inhibiting the VEGF-C/VEGFR-3 and Wnt pathways.
authors.affiliation: Respiratory Department, the Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Ming-zhu
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D042583:Lymphangiogenesis / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077150:Oxaliplatin; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D042582:Vascular Endothelial Growth Factor C; D000077150:Oxaliplatin; D040321:Vascular Endothelial Growth Factor Receptor-3; D007213:Indomethacin