阿司匹林抑制胃癌细胞生长及其机制探讨

Inhibition Effect of Aspirin on the Growth of Gastric Cancer and the Mechanism There-in Involved

目的 研究阿司匹林对 SGC- 790 1胃癌细胞生长的影响 ,并初步探讨其作用的分子机制。方法 采用 3H- Td R法及流式细胞术检测不同浓度阿司匹林对胃癌细胞 DNA合成及细胞周期的影响 ;用免疫细胞化学法检测阿司匹林对胃癌细胞 COX- 2表达的影响 ;Western blotting法及 EMSA法检测阿司匹林对胃癌细胞 c- fos表达及 AP- 1活化的影响。结果 胃癌细胞经不同浓度的阿司匹林作用后 ,其 3H- Td R掺入值明显降低 ,且与阿司匹林浓度呈高度负相关 ( r=- 0 .9,P<0 .0 5 )。细胞周期分析显示 ,阿司匹林主要作用于胃癌细胞 S期。免疫细胞化学染色显示 ,阿司匹林能下调胃癌细胞 COX- 2表达 ,且具有良好的量效关系。Western blotting检测表明 ,阿司匹林能降低胃癌细胞 c- fos蛋白的表达。EMSA分析显示 ,阿司匹林能有效抑制血清刺激的 AP- 1的 DNA结合活性。结论 阿司匹林能有效抑制胃癌细胞的生长 ,这种作用可能是其通过抑制胃癌细胞 c- fos表达以及 AP- 1活化 ,进而抑制COX-

Objectve To investigate the effect of aspirin on the growth of gastric cancer in vitro and the relevant mechanism. Methods The effect of aspirin on proliferation of SGC-7901 cells was measured by 3H-thymidine incorporation into DNA; the cell cycle was analyzed by flow cytometry. COX-2 protein was examined in SGC-7901 cells by immunohistochemistry. The expression of c-fos and the AP-1 activity were detected by immunoblotting and EMSA respectively. Results Aspirin decreased 3H-thymidine incorporation into SGC-7901 cells. The inhibition effect showed a good correlation with aspirin over a range of concentrations from 1×10 -1mol/L to 1×10 -5mol/L (r=0.9, P<0.01). Immunohistochemistry and immunoblotting indicated that aspirin effectively decreased COX-2 and c-fos expression in SGC-7901 cell. Aspirin could inhibit the AP-1 binding activation stimulated by fetal calf serum. Conclusion Aspirin is effective for inhibiting the growth of gastric cancer. The anti-neoplastic effect aspirin produces may involve the inhibition of COX-2 expression and AP-1 activity.