超声微泡介导VEGF反义寡核苷酸对裸鼠膀胱癌移植瘤生长的抑制作用  

Inhibitory effects of VEGF antisense oligodeoxynucleotides on bladder carcinoma in nude mice mediated by ultrasound microbubble

作　　者：高渝[1] 肖亚[1] 黄赤兵[1] 张唯力[2] 王志刚[3] 

机构地区：[1]第三军医大学附属新桥医院泌尿外二科,重庆400037 [2]重庆医科大学附属第二医院泌尿外科,重庆400010 [3]重庆医科大学医学影像学研究所,重庆400010

出　　处：《重庆医科大学学报》2009年第9期1176-1179,共4页Journal of Chongqing Medical University

摘　　要：目的:探讨利用超声辐照微泡造影剂介导血管内皮生长因子(Vascular endotheliar growth factor,VEGF)反义寡核苷酸(Antisense oligodeoxynucleotides,ASODN)对人膀胱癌裸鼠移植瘤的抑制效应。方法:人膀胱癌裸鼠皮下移植瘤模型建立后,将成瘤后的裸鼠随机分为3组:UM+ASODN组每只裸鼠尾静脉注射微泡造影剂与VEGF-ASODN混合物,并对移植瘤体用超声波进行辐照;UM组每只裸鼠尾静脉注射微泡造影剂并以同样的条件进行体外超声辐照;单纯对照组每只裸鼠尾静脉注射生理盐水,各组处理每隔2d进行1次,共计5次。观察裸鼠移植瘤生长情况,免疫组化SP法测Ki67、CD34、VEGF的表达,计算微血管密度、细胞增殖指数,TUNEL法测细胞凋亡指数。结果:UM+ASODN组裸鼠皮下肿瘤生长速度较对照组明显减慢,肿瘤组织VEGF的表达及微血管密度较对照组降低(P<0.05);与对照组相比,UM+ASODN组肿瘤细胞的凋亡增加(P<0.01),而细胞增殖减少(P<0.05)。结论:超声微泡介导的VEGF反义寡核苷酸转染能有效抑制膀胱癌裸鼠皮下移植瘤的生长。Objective：To investigate the effect of inhibition of vascular endothelial growth factor（VEGF） antisense oligodeoxynucleotides（ASODN） on human bladder carcinoma in nude mice mediated by ultrasound microbubble. Methods：The mice were randomly divided into 3 groups when transplantation tumor was established： For UM＋ASODN group, mixture of microbubble and VEGF-ASODN was inject into every mice from caudal vein plus ultrasound tumor local irradiation. For UM group, microbubble was inject into very mice from caudal vein plus local irradiation with the same condition. For control group, physiological saline was inject into every mice from caudal vein.The treatment was performed every 3 days with total 5 times.The volume change of mouse subcutane tumors was observed.Evaluate the expression of VEGF and CD34 and Ki67 with immunohistochemistry dyeing and calculate the microvessel density （MVD） and cell proliferation index;TUNEL assay was used to analyse the apoptosis of tumor cells. Results：The growth speed of nude mice tumor in UM＋ASODN group was obviously slower than control group; The expression of VEGF and The MVD in UM＋ ASODN group was lower than control group（P〈0.05）; To contrast with control group, the apoptosis of tumor in UM＋ ASODN group was increased（P〈0.01）, but the proliferate of tumor in UM＋ ASODN group was decreased（P〈0.05）. Conclusion：VEGF antisense oligonucleotides mediated by ultrasound microbubbe can efficiently inhibit the growth of human bladder carcinoma in nude mice.

关 键 词：超声微泡 血管内皮生长因子 膀胱肿瘤 反义寡核苷酸 

分 类 号：R737.1[医药卫生—肿瘤]