摘要
目的研究N-去硫酸肝素对人胃癌组织原位移植NOD-SCID小鼠转移模型的碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF）基因表达、血管形成和肿瘤转移影响。方法建立人胃癌组织原位移植NODSCID小鼠胃癌转移模型。移植后一周，20只小鼠随机分成两组，分别静脉注射生理盐水（0．9％氯化钠组）与10mg／kgN．去硫酸肝素（N-去硫酸肝素组），每周两次，共3周。第6周处死动物，观察肿瘤转移情况，免疫组织化学检测肿瘤组织微血管密度表达，荧光定量PCR检测肿瘤组织bFGF基因mRNA表达。结果0．9％氯化钠溶液组10只小鼠9只有肿瘤转移，N-去硫酸肝素组10只小鼠只有2只转移，两组间差异有统计学意义（P〈0．05）。未发现出血等不良反应。0．9％氯化钠溶液组平均微血管密度为9．1±3．4，N-去硫酸肝素组为4．7±1．8，两组间差异有统计学意义（t=3．617，P〈0．05）。荧光定量PCR测定显示，N-去硫酸肝素组bFGF mRNA（2．60±0．56％）相对表达量较0．9％氯化钠溶液组（30．65±6．84％）低，两组差异有统计学意义（t=4．08，P〈0．01）。结论 N-去硫酸肝素通过抑制肿瘤组织bFGF基因表达和血管生成，抑制肿瘤转移。N-去硫酸肝素无明显出血等不良反应。
Objective To investigate the effect of N-desulfated heparin on tumor metastasis, tumor angiogenesis and basic fibroblast growth factor（bFGF） gene expression of orthotopically implanted human gastric carcinoma in NODSCID mice. Methods Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of the NOD-SCID mice, Twenty mice were randomly divided into two groups which received either intravenous injection of 0.9% NaC1 solution（0.9%NaCl solution group） or 10 mg/kg N-desulfated heparin （N-desulfated heparin group） twice a week for three weeks. Mice were sacrificed six weeks after tumor implantation. Tissues from stomach and other organs were obtained for histopathological evaluation. The intratmnoral microvessel density （MVD） in tumor was evaluated immunohistochemically. Real time PCR was used to detect bFGF mRNA expression. Results The tumor metastasis rates were 9/10 in 0.9% NaC1 solution group and 2/10 in N-desulfated heparin group（ P 〈 0. 05）. MVD was 9.1 ± 3.4 in 0.9% NaCl solution group and 4.7 ± 1.8 in N-desulfated heparin group （ t = 3.617,P 〈0.05）. bFGF mRNA expression was lower in N-desulfated heparin group（2.60 ±0. 56 % ）than that in 0. 9 % NaCl solution group （30.65 ± 6.84 % ）. Conclusion N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting tumor bFGF gene expression and tumor angiogenesis with no obvious anticoagulant activity.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2008年第1期78-81,共4页
Chinese Journal of Medical Genetics
基金
上海市卫生局面上基金（034045）
