舒林酸对胃癌种植瘤的抑制作用及血管形成的影响

Inhibitory Effects of Sulindac on Xenograf Growth and Angiogenesis in Gastric Cancer

背景与目的:观察舒林酸的体内抗胃癌生长作用,并探讨舒林酸与胃癌血管生成的关系及其作用机制。材料与方法:建立人胃癌细胞BGC-823裸鼠种植瘤模型,随机分成舒林酸治疗组(12 mg/kg)、舒林酸预防组(8 mg/kg)、维生素C对照组(Vit C 20mg/kg)和空白对照组(生理盐水),共4组,给予舒林酸干预;用免疫组化检测胃癌移植瘤中COX-2、VEGF的表达和微血管密度(MVD值);用TUNEL法检测凋亡。结果:舒林酸抑制胃癌种植瘤生长,舒林酸治疗组和舒林酸预防组的肿瘤体积从第2周开始明显小于对照组(P<0.05),直到第35 d实验结束时舒林酸组与2个对照组相比,种植瘤体积均保持被明显抑制,差异均具有统计学意义(P<0.05)。肿瘤组织的凋亡指数:舒林酸治疗组为11.6,舒林酸预防组为10.4,维生素C对照组为3.5,空白对照组为3.1,舒林酸组高于对照组(P<0.05);MVD值:舒林酸治疗组为5.4,舒林酸预防组为9.0,维生素C对照组为19.6,空白对照组为20.7,舒林酸组显著低于对照组(P<0.01)。免疫组化结果:舒林酸组肿瘤组织COX-2蛋白和VEGF蛋白的阳性表达率均低于对照组(P<0.05)。结论:舒林酸在体内的抗胃癌效应显著,其机制可能涉及抑制胃癌细胞增殖,促进细胞凋亡及减少肿瘤新生血管的生成。

BACKGROUND AND AIM: To investigate the effects and mechanisms of sulindac on mice xenograft,angiogenesis and biologic behaviour of gastric cancer.MATERIALS AND METHODS: Twenty athymic xeograft models with human gastric cancer cell BGC-823 were established and randomly divided into four groups,sulindac treated group(12 mg/kg),sulindac preventive group(8 mg/kg),vitamin C group(Vit C 20 mg/kg) and control group.Immunohistochemistry was used to detect the expression of COX-2,VEGF and MVD in xenografts cells.TUNEL technique was applied to examine apoptosis.RESULTS: The growth of xenografts were markedly depressed by two weeks of sulindac treatment.The xenografts volume of sulindac-treated group and sulindac-preventive group were(57.2±3.2) mm3 and(77.8±6.7) mm3,respectively significantly smaller than those of vitamin C group and control group[(120.6±12.17) mm3 and(87.7±29.0) mm3 respectively,P<0.05].The xenograft volume maintained the difference until the experiment was finished.In vitamin C and control groups,the xenograft,apoptosis indexes(3.5 and 3.1,respectively) were lower than those in sulindac-treated and sulindac-preventive groups(11.6 and 10.4,respectively,P<0.05).Compared with vitamin C and control groups(19.6 and 20.7),the microvessel densities were remarkedly reduced in sulindac-treated and sulindac preventive groups(5.4 and 9.0,respectively,P<0.01).Compared with vitamin C and control groups,the expression of COX-2 and VEGF decreased markedly in sulindac-treated and sulindac-preventive groups(P<0.05).CONCLUSION: Sulindac had obvious anti-cancer effects in vivo against gastric cancer.The mechanism ofits'anti-cancer effects may include suppressing proliferation,inducing apoptosis,and reducing angiogenesis.