癌变·畸变·突变 ›› 2008, Vol. 20 ›› Issue (5): 346-349.doi: 10.3969/j.issn.1004-616x.2008.05.003

• 论著 • 上一篇    下一篇

舒林酸对胃癌种植瘤的抑制作用及血管形成的影响

汪向明1/ 于东红2/ 王 萍2/ 张 帆1/ 蔡兆根2/ 周 蕾2/ 承泽农2   

  1. 1.皖南医学院弋矶山医院病理科,安徽 芜湖 241001;2.蚌埠医学院病理教研室,安徽 蚌埠 233030
  • 收稿日期:2007-12-26 修回日期:2008-03-19 出版日期:2008-09-30 发布日期:2008-09-30

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

WANG Xiang_ming1,YU Dong_hong2,,WANG Ping2,ZHANG Fan1,CAI Zhao_gen2, ZHOU Lei2, CHENG Ze_nong2   

  1. 1.Department of Pathology, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui; 2. Department of Pathology,Bengbu Medical College,Bengbu 233030, Anhui, China
  • Received:2007-12-26 Revised:2008-03-19 Online:2008-09-30 Published:2008-09-30

摘要: 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 20 mg/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。

关键词: 胃癌, 裸鼠, 舒林酸, 环氧合酶2, 血管形成

Abstract: 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 of its'anti_cancer effects may include suppressing proliferation, inducing apoptosis, and reducing angiogenesis.

Key words: gastric tumor, nude mice, sulindac, cyclooxygenase_2, angiogenesis