| 谭妍迪,赵云,刘朝奇,周军,郑智唯,马瑶,姜矜君.超声介导载sPD-1和miR-206基因纳米微泡协同抑制小鼠H22肝癌皮下移植瘤[J].中国医学影像技术,2019,35(9):1315~1320 |
| 超声介导载sPD-1和miR-206基因纳米微泡协同抑制小鼠H22肝癌皮下移植瘤 |
| Ultrasound-mediated sPD-1 and miR-206 gene nanoscale microbubbles synergistic inhibition of H22 hepatoma subcutaneous xenografts in mice |
| 投稿时间：2019-02-13 修订日期：2019-07-15 |
| DOI：10.13929/j.1003-3289.201902029 |
| 中文关键词: 癌,肝细胞 微气泡 纳米粒子 微RNAs 超声检查 |
| 英文关键词:carcinoma, hepatocellular microbubbles nanoparticles microRNAs ultrasonography |
| 基金项目:宜昌市重点实验室（三峡大学）开放基金项目（2017KNX06）、三峡大学学位论文培优基金项目（2019SSPY111）。 |
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| 中文摘要: |
| 目的 探讨超声介导载可溶性程序性死亡因子1（sPD-1）联合miR-206纳米微泡对小鼠H22肝癌皮下移植瘤的干预效果。方法 自制载sPD-1和miR-206基因的纳米微泡，构建H22肝细胞癌皮下移植瘤小鼠模型，并将模型小鼠随机分为模型组、空微泡组、miR-206微泡组、sPD-1微泡组、联合组（给予miR-206微泡组及sPD-1微泡），分别每2天经尾静脉给予生理盐水及相应的微泡，每次注射后给予超声辐照瘤体治疗1次。5次治疗后取小鼠肿瘤组织，测量肿瘤质量及体积，计算肿瘤体积及质量抑瘤率，HE染色观察肿瘤组织病理变化，免疫组织化学法检测小鼠肿瘤组织Bax、Bcl-2蛋白表达，半定量PCR检测Bax、Bcl-2、c-met、γ干扰素（IFN-γ）、程序性死亡因子-1配体（PD-L1）mRNA表达，实时荧光定量PCR检测miR-206表达。结果 制备的纳米微泡呈球形，分布均一。与模型组比较，各组肿瘤体积、肿瘤质量均降低，体积抑瘤率及质量抑瘤率均升高（P均<0.05）；上述变化以联合组为著（P均<0.05）。与模型组比较，其余各组Bax蛋白和mRNA均高表达、Bcl-2蛋白和mRNA均低表达，以联合组为著（P均<0.01）。各组小鼠肿瘤组织Bax、Bcl-2、c-met、PD-L1、IFN-γ、miR-206 mRNA表达差异均有统计学意义（P均<0.01）。结论 超声介导载sPD-1和miR-206纳米微泡可协同抑制小鼠H22肝癌皮下移植瘤生长。 |
| 英文摘要: |
| Objective To investigate the effect of ultrasound-mediated soluble programmed cell death 1 receptor (sPD-1) and miR-206 loaded nanoscale microbubbles on H22 hepatoma subcutaneous xenografts in mice. Methods sPD-1 and miR-206 loaded nanoscale microbubbles were prepared. The mice models of H22 hepatoma xenografts were established and randomly divided into model group, microbubble control group, miR-206 microbubble group, sPD-1 microbubble group and combined group (miR-206 and sPD-1 microbubbles). Mice in each group (each n=8) were treated with normal saline or corresponding nanoscale microbubbles every 2 days by injection via tail vein, and then irradiated by ultrasound once after every injection. Tumor tissues were obtained after being treated 5 times. Tumor volume and quality were measured, the volume and quality inhibitory rates were calculated. HE staining was used to observe pathological changes of the tumors. The expressions of Bcl-2, Bax proteins were detected by immunohistochemistry. The expressions of Bcl-2, Bax, c-met, interferon-γ (IFN-γ) and programmed cell death 1 receptor ligand (PD-L1) mRNA were detected with RT-PCR. Quantitative real-time fluorescence PCR was used to detect the expression of miR-206. Results The nanoscale bubbles were spherical and distributed uniformly. Compared with model group, tumor volume and quality decreased in other groups, and the volume and quality inhibitory rates increased (all P<0.05), especially in combined group (all P<0.05). Compared with model group, the Bax protein and mRNA expressions both increased, whereas the Bcl-2 protein and mRNA expressions decreased in other groups, especially in combined group (all P<0.01). There were significant differences of Bax, Bcl-2, c-met, PD-L1, IFN-γ and miR-206 mRNA in tumor tissues among each group (all P<0.01). Conclusion Ultrasound-mediated sPD-1 combine miR-206 loaded nanoscale microbubbles can synergistically inhibit H22 hepatoma xenografts in mice. |
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