尼美舒利对胃癌抑制作用的实验研究

THE INHIBITORY EFFECT OF NIMESULIDE ON GASTRIC CANCER CELLS

为比较尼美舒利与吲哚美辛抑制胃癌的作用及比较尼美舒利对COX 2反义核酸转染前后胃癌细胞生物学行为的影响 ,并探讨其抗癌作用机制 ,用不同浓度尼美舒利和吲哚美辛与SGC790 1共孵育 ;尼美舒利与SGC790 1、790 1 P、790 1 AS共孵育 ,MTT法检测细胞活性。SGC790 1、790 1 P、790 1 AS各自分为尼美舒利组和对照组 ,FACS检测各组细胞周期。电镜观察SGC790 1、790 1 AS及与尼美舒利共孵育后SGC790 1的超微结构。结果显示 ,尼美舒利和吲哚美辛均可抑制胃癌体外增殖 ,效应呈剂量依赖性 ;尼美舒利对 790 1 AS比对亲本细胞的抑制率减少 (P<0 0 5 ) ,使胃癌G1期细胞比例增加(SGC790 1:73 5 %比 5 6 1% ;790 1 AS :76 7%比 66 5 % )。超微结构显示 ,尼美舒利作用的SGC790 1和 790 1 AS分化上发生良性转化 ,且出现凋亡。表明尼美舒利可抑制胃癌细胞体外增殖 ,其作用是COX 2依赖的。抑制胃癌的可能机制之一是抑制COX 2活性 ,进而影响细胞周期使之阻滞于G1期 。

The aims of this study were to compare the inhibitory effect of nimesulide and indomethacin on gastric cancer cells, to investigate the effect of nimesulide on SGC7901 and 7901-AS, and to evaluate its probable mechanism. After incubated with nimesulide (0～200μmol/L) or indomethacin (0～25μmol/L), the proliferation of gastric cancer cells was measured by MTT assay. The cell cycle of SGC7901, 7901-P, 7901-AS was respectively observed after being incubated with nimesulide and vehicle control, by using fluorescence activated cell sorter (FACS). Ultramicrostructure of gastric cancer cells (SGC7901,7901-AS,SGC7901+nimesulide) was observed by electronmicroscopy. The results showed that by MTT assay nimesulide, as indomethacin, had dose-dependent inhibitory effects on proliferation of gastric cancer cells. Compared to the inhibitory effect of nimesulide on SGC7901, it was less on 7901-AS (P<0.05). Nimesulide resulted in G 1 delay. The percent of G 1 cells was 73.5% (vs 56.1%) in SGC7901 cells, and 76.7% (vs 66.5%) in 7901-AS cells. Nimesulide also induced differentiation and apoptosis of gastric cancer cells. Therefore, nimesulide as well as indomethacin can dose-dependently inhibit the proliferation of gastric cancer cells. The inhibitory effect is COX-2-dependent. By inhibiting the activation of COX-2 and influencing cell cycle, differentiation and apoptosis of gastric cancer cells are induced, and it might be one of the mechanisms that nimesulide inhibits gastric cancer.