环氧化酶2抑制剂对胃癌转移抑制作用的实验研究

Inhibition of cyclooxygenase-2 on metastasis of orthotopic implantatiom of human gastric carcinoma

目的研究环氧化酶2抑制剂对人胃癌组织原位移植非肥胖性糖尿病(NOD)重度联合免疫缺陷(SC ID)小鼠转移模型的肿瘤转移抑制剂、血管生成和血管内皮生长因子(VEGF)表达的影响。方法建立人胃癌组织原位移植NOD SC ID小鼠胃癌转移模型,40只小鼠均分成两组。移植后1周,分别静脉注射0.9%氯化钠溶液(0.9%氯化钠溶液组)50 mg/(kg.d)环氧化酶2抑制剂(尼美舒利组),每周2次,共2周。第5周处死动物,观察肿瘤转移情况,免疫组化法检测肿瘤组织微血管密度、VEGF表达,荧光定量PCR检测肿瘤组织VEGF mRNA表达。结果0.9%氯化钠溶液组20只小鼠18只有肿瘤转移,尼美舒利组20只小鼠只有5只转移,两组间差异有统计学意义(P<0.05)。0.9%氯化钠溶液组平均微血管密度为9.5±2.9,尼美舒利组为3.9±2.1,两组间差异有统计学意义(P<0.05)。0.9%氯化钠溶液组18只小鼠VEGF阳性表达,明显高于尼美舒利组的5只(P<0.05)。荧光定量PCR测定显示,尼美舒利组VEGFmRNA(C t:20.1±2.0)表达较0.9%氯化钠溶液组(C t:15.9±1.8)低,两组间差异有统计学意义(尼美舒利,P<0.05)。结论环氧化酶2抑制剂尼美舒利通过抑制肿瘤组织VEGF表达和血管生成,抑制肿瘤转移,尼美舒利无明显出血等不良反应。

Objective To investigate the effect of a selective cyclooxygenase -2 inhibitor on tumor metastasis, tumor angiogenesis,and vascular endothelial growth factor（VEGF） of orthotopic implantated human gastric carcinoma in non -obesity diabetes（NOD） severe combined immune deficiency（SCID） mice. Methods Human gastric cancer SGC -7901 tissues were orthotopically implanted into the stomach of the NOD SCID mice. Forty mice were randomly divided into two groups which received either intravenous injections of 0. 9% NaCl solution （0. 9% NaCl solution group）50 mg/（ kg · d） nimesulide （ nimesulide group） twice weekly for two weeks. Mice were sacrificed five weeks after implantation. Tissues from stomach and other organs were obtained for histopathological evaluation. The intratumoral microvessel density（ （MVD） and VEGF protein expression in tumor were evaluated immunochemically. Real time PCR technique was used to detect VEGF mRNA expression. Results The tumor metastasis rates were 18/20 in 0. 9% NaCl solution group and 5/20 in nimesulide group （ P 〈0.05）. MVD was 9. 5 ±2.9 in 0.9% NaCl solution group and 3.9 ±2.1 in nimesulide group（ P 〈0.05）. VEGF protein expression was 90% in 0. 9% NaCl solution group and 25% in nimesulide group（ P 〈 0.05 ）. VEGF mRNA expression was lower in nimesulide group（ Ct ：20.1 ± 2.0） than that in 0.9% NaC1 solution group （ Ct ： 15.9 ± 1.8, P 〈 0.05 ）. Conclusion Nimesulide can inhibit the metastasis or gastric cancer through inhibiting tumor VEGF expression, and tumor angiogenesis with no obvious anticoagulant activity.