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 ß-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, ß-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 ß-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 ß-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 ß-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 ß-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 ß-catenin. Oxaliplatin can significantly inhibit the growth of lung cancer xenografts in nude mice, and the expression of survivin and ß-catenin. Nimesulide in combination with oxaliplatin enhances the antitumor effect of oxaliplatin.