非甾体类抗炎药对胃癌细胞增殖的抑制作用

The inhibitory effect of nonsteroid anti-inflammatory drugs on gastric cancer

目的 比较 7种常用非甾体类抗炎药对胃癌细胞增殖、凋亡及其体内成瘤性的影响。方法 噻唑蓝 (MTT)比色法检测胃癌细胞的增殖 ;流式细胞术检测凋亡的胃癌细胞 ;裸鼠移植瘤实验检测胃癌细胞体内成瘤性。结果 5种非甾体类抗炎药对胃癌细胞增殖有抑制作用 ,且呈剂量依赖关系 ,以塞来昔布作用最显著 ,对SGC790 1细胞抑制率为 (43.4± 1.6 5 ) % ,对AGS细胞抑制率为 (45 .1±2 .74 ) %。布洛芬和萘普生对细胞增殖无作用。塞来昔布、尼美舒利、舒林酸、吲哚美辛对裸鼠移植瘤的抑瘤率分别为 (93.8± 0 .97) % ,(93.1± 1.78) % ,(89.3± 2 .0 7) %和 (89.9± 5 .6 1) %。流式细胞术检测塞来昔布组和吲哚美辛组凋亡细胞所占比例分别增加了 30 .4 % (34.5 %比 4 .1% )和 2 3.9% (2 8.0 %比4 .1% )。结论 塞来昔布抑瘤作用最明显 ,其次为尼美舒利、舒林酸、吲哚美辛 ,而布洛芬和萘普生作用不明显。诱导细胞凋亡可能是非甾体类抗炎药抑制胃癌的主要机制之一。

Objective To compare the effect of seven commonly used nonsteroidal anti inflammatory drugs (NSAIDs) on proliferation, apoptosis, and neoplasmagenesis of gastric cancer cells in vivo. Methods Gastric cancer cell lines were treated with NSAIDs (aspirin 0-400 μmol/L, indomethacin 0-25 μmol/L, and ibuprofen, naproxen, sulindac, nimesulide, celecoxib 0-200 μmol/L, respectively). Proliferation of the cells was detected by using MTT assay. Apoptosis of cells was measured by using fluorescence activated cell sorter (FACS). Nude mice bearing gastric cancer xenografts were administrated with NSAIDs (indomethacin 3 mg/kg, sulindac 8 mg/kg, nimesulide 6 mg/kg, celecoxib 15 mg/kg) for 30 days, and then the weight of implanted tumors was measured. Results There was a dose dependent inhibition of cell proliferation by majority of NSAIDs used, celecoxib the most, except for ibuprofen and naproxen. In nude mice, NSAIDs also showed a suppressive effect on tumor growth with inhibitory rate of celecoxib as (93.8±0.97)%, nimesulide (93.1±1.78)%, indomethacin (89.9±5.61)% and sulindac (89.3 ± 2.07)%. Once incubated with celecoxib and indomethacin, the gastric cancer cells went to apoptosis with an increase in percentage of apoptotic cells up to 30.4% and 23.9%, respectively. Conclusions Many NSAIDs, celecoxib in particular, appeared to be suppressive to gastric cancer cells with exception for ibuprofen and naproxen. Induction of apoptosis might be one of the mechanisms that NSAIDs inhibit gastric cancer.