超声微泡介导miR-34a联合DOX治疗小鼠U14皮下移植瘤的实验研究  

Experimental Study of Ultrasound Microbubble Mediated miR-34a combined with DOX on U14 Transplantation Tumor in Mice

作　　者：郑智唯 刘朝奇[1] 赵云[1] 熊海容 马瑶[1] 姜衿君 Zheng Zhiwei;Liu Chaoqi;Zhao Yun;Xiong Hairong;Ma Yao;Jiang Jinjun(Key Laboratory of Tumor Microenvironment and Immunotherapy, Three Gorges University School of Medicine, Yiehang, Hubei 443002, Chin)

机构地区：[1]三峡大学医学院肿瘤微环境与免疫治疗湖北省重点实验室,湖北省宜昌市443000

出　　处：《中国超声医学杂志》2018年第7期664-667,共4页Chinese Journal of Ultrasound in Medicine

基　　金：国家自然科学基金(No.81473461)

摘　　要：目的研究超声介导载miR-34a、DOX微泡对小鼠U14宫颈癌皮下移植瘤联合治疗效果。方法制备载miR-34a、DOX高分子微泡,检测一般性质;建立小鼠皮下移植瘤模型,随机分为:模型组、空微泡组、DOX微泡组、miR-34a微泡组、miR-34a联合DOX微泡组;超声微泡治疗小鼠皮下移植瘤,绘制肿瘤生长曲线图,计算抑瘤率;RT-PCR检测各组小鼠肿瘤组织miR-34a基因表达情况;免疫组织化学染色法检测肿瘤微血管密度(MVD)和凋亡蛋白Bcl-2、Bax表达情况。结果自制高分子微泡呈球形,分布均一,平均粒径1.87μm,包封率为46.24%,载药量为10.58%;与模型组相比,各治疗组肿瘤生长减慢,肿瘤质量体积显著下降,联合治疗效果更佳并与单一作用比较具有显著差异(P<0.05);聚合酶链式反应(RT-PCR)结果显示,miR-34a组和联合组肿瘤组织中miR-34a高表达;DOX组、miR-34a组和联合组免疫组织化学染色检测肿瘤微血管密度(MVD)降低,凋亡蛋白Bcl-2表达下调,Bax高表达,联合组更加明显(P<0.05)。结论超声微泡介导的miR-34a和DOX的共同递送可以实现肿瘤抑制的协同效应。Objective To evaluate the combined treatment effects of ultrasound-mediated miR-34a and DOX loaded microbubbles on U14 transplantation tumor in mice.Methods Preparation of miR-34a and DOX microbubbles were performed to detect the general properties.We established U14 transplantation tumor models in mice,then mice were divided into model group,empty microbubble group,DOX microbubble group,miR-34a microbubble group,combined group.Ultrasound microbubble treatment of mouse subcutaneous transplanted tumor,drawing the tumor growth curve,calculate the tumor inhibition rate.The expression of miR-34a gene was detected by RT-PCR,The expression of Bcl-2 and Bax,microvessel density（MVD）were detected by immunohistochemical staining.Results The microbubbles were spherical and distributed uniformly,The encapsulation efficiency of DOX-loaded microbubbles and drug loading were 46.24% and 10.58%.The tumor of each treated group grew slowly and the combination therapy was better and compared with the single effect（P〈0.05）.RT-PCR results show that the expression of miR-34a in miR-34a group and combined group was significantly higher than that in control group（P〈0.05）.Tumor microvessel density（MVD）was decreased,Bcl-2 expression was decreased,Bax expression was increased in DOX group,miR-34a group and combined group,Combined group are more obvious（P〈0.05）.Conclusions Co-delivery of DOX and miR-34a can achieve synergistic effects of tumor suppression by ultrasound microbubble.

关 键 词：超声微泡 MIR-34A U14细胞 移植瘤 

分 类 号：R445.1[医药卫生—影像医学与核医学] R737.33[医药卫生—诊断学]