Fang Hai-Ming, Mei Qiao, Xu Jian-Ming, Ma Wei-Juan
Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui Province, China.
World J Gastroenterol. 2007 May 28;13(20):2872-7. doi: 10.3748/wjg.v13.i20.2872.
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.
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.
Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 micromol/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 micromol/L) or nimesulide (100 micromol/L) for 12-96 h, which showed an obvious time-effect relationship (t=6.149, P<0.05; t=4.159, P<0.05, respectively). At the concentration of 10-500 micromol/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 dose-dependent and time-dependent manner (t=5.448, P<0.05; t=4.428, P<0.05, respectively).
5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.
探讨5-氨基水杨酸（5-ASA）联合尼美舒利对HT-29结肠癌细胞增殖的影响及其潜在机制。
采用噻唑蓝四氮唑溴盐（MTT）法研究药物（5-ASA、尼美舒利及其联合用药）对HT-29结肠癌细胞的抑制作用。分别通过TUNEL法和免疫细胞化学染色检测细胞凋亡和增殖情况。
在体外，10 - 1000微摩尔/升浓度的5-ASA或尼美舒利预处理均能以剂量依赖方式抑制HT-29结肠癌细胞增殖（t = 5.122，P < 0.05；t = 3.086，P < 0.05）。用5-ASA（100微摩尔/升）或尼美舒利（100微摩尔/升）预处理12 - 96小时，HT-29结肠癌细胞增殖抑制率也升高，呈现明显的时间效应关系（t = 6.149，P < 0.05；t = 4.159，P < 0.05）。在10 - 500微摩尔/升浓度时，HT-29结肠癌细胞凋亡率显著升高（t = 18.156，P < 0.001；t = 19.983，P < 0.001），而增殖细胞核抗原（PCNA）表达明显降低（t = 6.828，P < 0.05；t = 14.024，P < 0.05）。5-ASA联合尼美舒利比单独使用这两种药物更能以剂量和时间依赖方式抑制HT-29结肠癌细胞增殖（t = 5.448，P < 0.05；t = 4.428，P < 0.05）。
5-ASA和尼美舒利可能抑制HT-29结肠癌细胞增殖，联合使用这两种药物可能具有额外的化学预防潜力。
