血管内皮抑制素对Calu-6裸鼠移植瘤的生物学效应  

Biological effect of endostatin on transplanted human lung adenocarcinoma Calu-6 tumor in nude mice

作　　者：王晶[1] 黄纯[1] 魏熙胤[2] 战忠利[3] 孙慧[4] 杨毅[2] 李凯[1] 

机构地区：[1]天津肿瘤防治重点实验室天津肺癌诊治中心天津医科大学附属肿瘤医院肺内科,300060 [2]天津肿瘤防治重点实验室天津肺癌诊治中心天津医科大学附属肿瘤医院中心实验室,300060 [3]天津肿瘤防治重点实验室天津肺癌诊治中心天津医科大学附属肿瘤医院病理科,300060 [4]天津肿瘤防治重点实验室天津肺癌诊治中心天津医科大学附属肿瘤医院实验肿瘤室,300060

出　　处：《中华肿瘤杂志》2008年第4期266-269,共4页Chinese Journal of Oncology

基　　金：吴阶平基金会临床科研专项基金资助项目（04101002）

摘　　要：目的探讨血管内皮抑制素对Calu-6裸鼠移植瘤生长及新生血管形成的影响。方法在荷瘤裸鼠皮下注射不同剂量的血管内皮抑制素，观察注射后肿瘤体积的变化；应用免疫组化SABC法检测肿瘤组织中血管内皮生长因子（VEGF）、生存素（survivin）和环氧化酶-2（COX-2）蛋白的表达以及微血管密度（MVD）的变化；流式细胞术检测循环血管内皮细胞（CECs）的含量；应用逆转录聚合酶链反应（RT—PCR）和实时定量PCR检测外周血中CDl46和CDl05mRNA的表达。结果经血管内皮抑制素治疗后，荷瘤鼠肿瘤体积明显减小；肿瘤组织中VEGF、survivin和COX-2蛋白的表达以及MVD均下降，且各治疗组与阳性对照组间的差异均有统计学意义（均P〈0．05）；外周血中CECs、CDl46和CDl05mRNA的含量均明显下降；活化CECs的含量与肿瘤组织中survivin和VEGF的表达以及MVD的变化均呈正相关。结论血管内皮抑制素可通过下调移植瘤中VEGF、survivin和COX-2蛋白的表达以及减少MVD抑制肿瘤生长；活化CECs将可能作为理想的预测抗血管形成治疗预后的标记物应用于临床。Objective To assess the effect of endostatin on growth and neoplastic angiogenesis in transplanted human lung adenocarcinoma Calu-6 tumor in nude mice. Methods To treat Calu-6 tumorbearing mice with endostatin at different doses, and to record the changes of the tumor size. The expressions of survivin, VEGF, COX-2 and MVD in tumor tissue were examined by immunohistochemistry staining, circulating endothelial cells （CECs） by flow cytometry and mRNA of CD146 and CD105 by RT-PCR and real-time PCR. Results After endostatin treatment, the tumor size was conspicuously shrunk, and the expressions of survivin, COX-2 and VEGF protein and MVD in tumor tissue decreased concomitantly with the significant difference between each of trial groups and control group （ all P 〈 0.05 ）. Both CECs and mRNA of CD146 and CD105 diminished remarkably. A positive correlation between both exhibition and change of amount of activated CECs and survivin, VEGF expression and MVD count in tumor tissue was found. Conclusion Endostatin can decrease the expression of survivin, COX-2, VEGF and MVD, and to inhibit the growth of transplanted tumor. Activated CECs may probably serve as an ideal marker to predict the efficacy and prognosis of anti-angiogenesis therapy.

关 键 词：血管内皮抑制素 循环血管内皮细胞 生存素 血管内皮生长因子 微血管 密度 

分 类 号：R686[医药卫生—骨科学]