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目的观察环氧合酶2抑制剂在动物体内的抗胃癌生长作用并探讨其与胃癌血管生成的关系,研究其作用机制。方法建立人胃癌细胞SGC7901裸鼠种植瘤模型,随机分成三组,给予非甾体消炎药舒林酸和选择性环氧合酶2抑制剂塞来昔布干预;用免疫组化法检测细胞增殖(PCNA的表达)和微血管密度(VWF和CD34的表达),用TUNEL法检测凋亡。结果舒林酸和塞来昔布均显著抑制胃癌种植瘤的生长,两组肿瘤体积从第2周开始即显著小于对照组,对照组为(608.9±288.8)mm3,舒林酸组为(351.5±227.0)mm3,塞来昔布组为(108.3±105.4)mm3(P<0.01);细胞增殖指数对照组为17.5±8.3,舒林酸组为13.6±7.4,塞来昔布组为9.8±5.0,处理组明显低于对照组(P<0.05);三组凋亡指数分别为2.5±1.6、4.8±5.3和5.6±3.5,对照组低于处理组(P<0.05);微血管密度分别为5.6±3.0、2.8±2.2和2.5±2.3,处理组较对照组降低(P<0.01),但两处理组之间各项比较均未达显著差异。结论环氧合酶2抑制剂在体内具有显著抗胃癌效应,并可能与抑制血管生成有关,环氧合酶2抑制剂的抗癌机制可能为增加凋亡、抑制增殖及减少血管生成。
Objective To observe the anti-gastric cancer growth effect of cyclooxygenase-2 inhibitor in animal and explore its relationship with angiogenesis in gastric cancer and to study its mechanism. Methods The human gastric cancer cell SGC7901 xenografts model was established and randomly divided into three groups. The mice were given NSAID and celecoxib, a selective inhibitor of COX-2, and the cell proliferation was detected by immunohistochemistry (PCNA expression) and microvessel density (VWF and CD34 expression) were detected by TUNEL assay. Results Both sulindac and celecoxib significantly inhibited the growth of implanted tumor in gastric cancer. The tumor volume of the two groups was significantly lower than that of the control group from the second week, the control group was (608.9 ± 288.8) mm3, the sulindac group was (351.5 ± 227.0) mm3, and (108.3 ± 105.4) mm3 in celecoxib group (P <0.01). The cell proliferation index was 17.5 ± 8.3 in control group, 13.6 ± 7.4 in sulindac group, 9.8 ± in celecoxib group 5.0 in treatment group was significantly lower than that in control group (P <0.05). The apoptotic indexes in the three groups were 2.5 ± 1.6, 4.8 ± 5.3 and 5.6 ± 3.5 respectively, while those in control group were lower than those in control group (P <0.05) 5.6 ± 3.0, 2.8 ± 2.2 and 2.5 ± 2.3, respectively. The treatment group was lower than the control group (P <0.01), but there was no significant difference between the two treatment groups. Conclusions Cyclooxygenase 2 inhibitors have significant anti-gastric cancer effects in vivo and may be related to the inhibition of angiogenesis. Cyclooxygenase-2 inhibitors may have anti-cancer mechanisms of increasing apoptosis, inhibiting proliferation and decreasing angiogenesis.