去甲斑蝥素对裸鼠结肠癌移植瘤血管生成的影响及其机制  

Effect of Norcantharidin on Angiogenesis of Human Colon Cancer Xenografts in Nude Mice and Its Possible Mechanism

作　　者：袁昌劲[1] 余涛[1] 侯风刚[2] 李丹[3] 刘礼[1] 吕秀玮[1] 任丽[1] 

机构地区：[1]华中科技大学同济医学院附属武汉中心医院中西医结合肿瘤科,武汉430014 [2]上海中医药大学附属上海市中医医院肿瘤科,上海200071 [3]武汉大学人民医院药学部,武汉430060

出　　处：《华中科技大学学报（医学版）》2013年第3期278-281,298,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的观察去甲斑蝥素(NCTD)对人结肠癌裸鼠移植瘤血管生成及瘤体血管内皮细胞生长因子(VEGF)、内皮细胞钙黏蛋白(VE-Cd)、基质金属蛋白酶2(MMP-2)表达的影响,以探讨NCTD影响血管生成的可能机制。方法裸鼠皮下移植人结肠癌细胞(HCT116)瘤块建立人结肠癌皮下移植瘤模型,随机分为模型组,NCTD高、中、低剂量组和氟尿嘧啶(5-Fu)组。分别腹腔注射生理盐水、NCTD 8、5、2mg/kg和5-FU 20mg/kg,每周2次,连续给药3周。给药结束后剥取瘤体并称重,常规石蜡包埋、制片,采用免疫组化法分析瘤体内微血管密度(MVD)以及VEGF、VE-Cd、MMP-2等促血管生成因子的表达水平。结果与模型组相比,经NCTD干预的荷瘤裸鼠生长状态基本不受影响,但瘤体生长受到抑制,瘤内微血管密度降低,VEGF、VE-Cd、MMP-2蛋白表达减少,且此效应随剂量增大而增强。结论 NCTD在不影响荷瘤裸鼠生长状态的前提下,对人结肠癌裸鼠皮下移植瘤的生长和瘤内微血管的形成具有抑制作用,其机制跟下调VEGF、VE-Cd、MMP-2等促血管生成因子的表达有关。Objective To investigate the effects of norcantharidin on angiogenesis of human colon cancer xenografts in nude mice and the underlying mechanism.Methods The mouse model of subcutaneous xenograft was established with human colon cancer cells（HCT116）.All tumor-bearing nude mice were randomly divided into control group,high-,medium-,low-dose NCTD-treated groups and 5-fluorouracil（Fu）group.Mice in each group were intraperitoneally injected with normal saline（0.5 mL）,NCTD（8,5or 2mg/kg）,5-Fu（20mg/kg）respectively twice a week for 3weeks.The tumor xenografts were harvested and measured for their weights.Immunohistochemistry was used to detect the microvessel density（MVD）and expressions of endothelial growth factor（VEGF）,vascular endothelial cell cadherin（VE-Cd）,matrix metalloproteinase-2（MMP-2）.Results NCTD inhibited the tumor growth,decreased the MVD and the expressions of VEGF,VE-Cd and MMP-2 in a dose-dependant manner.These indices in NCTD-treated groups were significantly decreased when compared with the control group.Conclusion NCTD can inhibit the growth of tumor xenografts and angiogenesis of human colon carcinoma,which is associated with the down-regulation of the expressions of VEGF,VE-Cd and MMP-2 proteins.

关 键 词：去甲斑蝥素 结肠癌 血管生成 血管内皮生长因子 内皮细胞钙黏蛋白 基质金属蛋白酶2 

分 类 号：R735.3[医药卫生—肿瘤]