血管内皮抑制素对Calu-6裸鼠移植瘤的生物学效应

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CD146和CD105 mRNA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、CD146和CD105 mRNA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.

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

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 tumor-bearing 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.