人canstatin基因治疗人食管癌裸鼠移植瘤的实验研究

背景与目的：Canstatin是一种新内源性血管生成抑制剂，以往的研究显示canstatin能有效的抑制肿瘤的生长，作用甚至强于endostatin。本研究将探讨人canstatin基因对人食管鳞状细胞癌移植瘤模型的抑制作用。方法：应用人食管癌细胞株KYSE150建立移植瘤模型。将裸鼠随机分成3组：腺病毒携带的canstatin基因组（Ad—GFP—canstatin）、腺病毒携带的绿色荧光蛋白组（Ad—GFP）和磷酸盐缓冲液组（PBS）。治疗期间测量皮下移植瘤的长径和短径；30d后处死裸鼠，取下肿瘤行常规病理切片，观察药物的毒性反应；检测肿瘤组织中caspase-3、内皮细胞生长因子受体1（fetal liver kinase-1，Flk-1）和血管内皮生长因子（vascular endothelial growth factor，VEGF）的表达和微血管密度（microvessel density，MVD）。结果：第二次注射病毒后3d，canstatin基因治疗组肿瘤体积显著小于其余两组（P〈0．05），治疗第6天抑瘤率达到61％；HE染色显示：各组肿瘤组织中都有坏死．尤其在canstatin基因治疗组坏死更加明显；canstatin基因治疗组caspase-3表达高于空载体组和对照组（P〈0．05）；Flk-1的表达低于空载体组和对照组（P〈0．05）：VEGF的表达3组相比差异无统计学意义（P〉0．05）：canstatin基因治疗组MVD低于空载体组和对照组（P〈0．05）。结论：人canstatin基因对人食管癌移植瘤的生长具有抑制作用，作用机制可能是降低Flk-1的表达进而抑制肿瘤的血管生成，抑制肿瘤的生长。

In vivo antitumor effect of canstatin gene on human esophageal carcinoma xenografts in nude mice

Background and Objective： Canstatin is a newly discovered endogenous inhibitor of angiogenesis. Previous study has shown that canstatin can efficiently suppress the growth of human cancers, even more potent than endostatin. This study was to investigate the antitumor effects of canstatin gene on human esophageal carcinoma xenografts. Methods： Tumor xenografts were induced with KYSE150 cells in BALB/c nude mice, and randomized into three groups： PBS, adenovirus green fluorescent protein （Ad-GFP）, and Ad-GFP-canstatin groups. During treatment, tumor size was measured. The mice were killed 30 days later to observe tumor morphology. The expression of vascular endothelial growth factor （VEGF）, fetal liver kinase-1 （FIk-1）, caspase-3 and microvessel density （MVD） were detected by immunohistochemistry. Results： Compared with that in Ad-GFP and PBS groups, tumor growth in Ad-GFP-canstatin group was significantly suppressed in the first week after gene transfection. The inhibition rate of tumor growth was up to 61% at the sixth day. Necrotic regions were observed in all groups, especially in Ad-GFP-canstatin group. Compared with those in Ad-GFP and PBS groups, caspase-3 expression in Ad-GFP-canstatin group was higher （P〈0.05）, while FIk-1 expression and MVD was lower （P〈0.05）. There was no obvious difference in VEGF expression among the three groups. Conclusion： Canstatin can inhibit the growth of human esophageal carcinoma by suppressing angiogenesis via down-regulating FIk-1 expression.