塞来昔布诱导人胃癌细胞凋亡抑制新生血管形成

Celecoxib induces apoptusis and inhibites angiogenesis in gastric cancer

目的探讨环氧合酶2（COX-2）抑制剂塞来昔布对人胃癌细胞增殖和新生血管形成的抑制作用。方法将59例胃癌患者随机分为试验组（37例）和对照组（22例），试验组术前给予常规剂量塞来昔布，共7d，然后行手术治疗；对照组行单纯手术治疗。免疫组化法检测胃癌组织中COX-2和血管内皮生长因子（VEGF）的表达及微血管密度（MVD），DNA末端原位标记染色法检测胃癌细胞凋亡。以20例健康人作为正常对照。结果试验组胃癌细胞凋亡率为7．1％±1．0％，显著高于对照组（6，2％±0．9％，P〈0．05）。试验组和对照组中，COX-2阳性表达分别为16例（43．2％）和17例（77．3％），VEGF阳性表达分别为17例（45．9％）和16例（72．7％），差异均有统计学意义（P〈0．05）。试验组MVD为30．48±5．02，显著低于对照组（38．98±4．58，P〈0．05）。结论塞来昔布可诱导人胃癌细胞凋亡，抑制胃癌新生血管形成。

Objective The aim of this study was to explore the effect of celecoxib, a cyclooxygenase-2 inhibitor, on induction of apoptosis and inhibition of angiogenesis in gastric cancer. Methods Fifty nine gastric cancer patients were randomly divided into 2 groups ： celecoxib group （ n = 37） and control group （ n = 22）. The patients in the celecoxib group were treated orally with celecoxib 200 mg twice daily for 7 days before resection. The patients in the control group received surgical resection alone. Another group of 20 healthy subjects were recruited as normal control. The number of apoptotic tumor cells was measured by terminal deoxynucleotidyl transferse-mediated dUTP nick end labeling （TUNEL）. The expression of COX-2, VEGF and the microveosel density （MVD） were evaluated by immunohistochemistry. Results The TUNEL results showed an increase of apoptosis in the tumor cells after celecoxib treatment in comparison with that in the control group （7.1% ± 1.0% vs. 6.2% ± 0.9% , P 〈 0.05 ）. The expression level of COX-2 and VEGF in the gastric cancer tissues was significantly decreased in the celecoxib group compared with those in the control group （ P 〈 0.05 ）. Furthermore, MVD was also significantly lower in the celecoxib group when compared with that in the control group （ 30.48 ± 5.02 vs. 38.98± 4.58, P 〈 0.05 ）. Conclusion Oral intake of celecoxib can induce apoptosis and suppress angiogenesis in gastric cancer. It may become an effective agent in the treatment of gastric cancer.