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To investigate the combined effects of indomethacin and oxaliplatin on expressions of epidermal growth factor receptor (EGFR), E-cadherin (E-cad), intercellular adhesion molecule-1 (ICAM-1) and CD44v6 related to lymph node metastasis of human lung cancer cell lines. Human lung adenocarcinoma A549 cells were inoculated subcutaneously into the left armpit of nude mice to establish human lung cancer xenografts. The mice were randomly divided into control group, indomethacin group, oxaliplatin group and combination therapy group, which were treated with sterile distilled water, indomethacin, oxaliplatin and indomethacin combined with oxaliplatin, respectively. After 42 days, the mice were sacrificed. The immunohistochemistry and reverse transcription polymerase chain reaction were used to detect the expressions of EGFR, E-cad, ICAM-1 and CD44v6 in tumor tissues. Compared to control group, the protein and mRNA expressions of EGFR, ICAM-1 and CD44v6 in the indomethacin, oxaliplatin, and combination therapy groups were significantly reduced (P<0.05) and the protein and mRNA expressions of E-cad expression were significantly increased (P<0.05). Compared to indomethacin group and oxaliplatin group, the protein and mRNA expressions of EGFR, ICAM-1 and CD44v6 in combination therapy groups were significantly reduced (P<0.05), and the protein and mRNA expressions of E-cad expression were significantly increased (P<0.05). There was no significant difference between indomethacin and oxaliplatin groups. Indomethacin and oxaliplatin have synergistic effect on expressions of lymph node metastasis related factors in lung cancer cell lines. [ABSTRACT FROM AUTHOR]