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AIM:To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms.METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining, respectively.RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122, P ＜ 0.05; t = 3.086, P ＜0.05, respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100μmol/L) for 12-96 h, which showed an obvious timeeffect relationship (t = 6.149, P ＜ 0.05; t = 4.159, P＜ 0.05, respectively). At the concentration of 10-500μmol/L, the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156, P ＜ 0.001; t =19.983, P ＜ 0.001, respectively), while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828, P ＜ 0.05; t = 14.024, P ＜ 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dosedependent and time-dependent manner (t = 5.448, P ＜0.05; t = 4.428, P ＜ 0.05, respectively).CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.