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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(SCID)小鼠转移模型的肿瘤转移、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 SCID小鼠胃癌转移模型,40只小鼠随机分成2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~(-1)·d~(-1)环氧化酶2抑制剂(尼美舒利组),每周2次,共2周。第5用处死动物,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只小鼠中18只有肿瘤转移,尼美舒利组20只小鼠只有5只有转移,两组闯有显著差异(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±2.1,两组间有显著差异(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VEGF mRNA(Ct:20.12±1.96)表达较0.9%氯化钠溶液组(Ct:15.92±1.76)低,两组间有显著差异(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 effects of cyclooxygenase-2 inhibitor on tumor metastasis, angiogenesis and expression of vascular endothelial growth factor (VEGF) in metastatic non-obese diabetic model (NOD) mice with gastric cancer Impact. Methods: Gastric cancer metastasis model of NOD SCID mice was established by in situ transplantation of human gastric cancer tissue. Forty mice were randomly divided into two groups. One week after transplantation, rats were treated with 0.9% sodium chloride solution (0.9% sodium chloride solution) 50 mg · kg -1 d -1 cyclooxygenase 2 inhibitor (nimesulide Lee group), 2 times a week, a total of 2 weeks. The animals were sacrificed on the 5th day to observe the tumor metastasis. The microvessel density and VEGF expression in the tumor tissue were detected by immunohistochemistry. The expression of VEGF mRNA in the tumor tissue was detected by fluorescence quantitative PCR. RESULTS: Twenty-eight of 20 mice in the 0.9% sodium chloride solution group had tumor metastasis, and only 5 of 20 mice in the nimesulide group had metastasis. There was significant difference between the two groups (P <0.05). The mean microvessel density in the 0.9% sodium chloride solution group was 9.5 ± 2.9 and in the nimesulide group was 3.9 ± 2.1, with significant differences between the two groups (P <0.05). The VEGF expression in 18 mice in 0.9% sodium chloride solution group was significantly higher than that in nimesulide group (P <0.05). Fluorescence quantitative PCR showed that the expression of VEGF mRNA in Nimesulide group (Ct: 20.12 ± 1.96) was lower than that in 0.9% sodium chloride solution group (Ct: 15.92 ± 1.76), with significant difference between the two groups (P <0.05). CONCLUSION: Nimesulide, a cyclooxygenase 2 inhibitor, inhibits tumor metastasis by inhibiting VEGF expression and angiogenesis, and nimesulide has no obvious hemorrhage and other adverse reactions.