长循环 miR-135a 阳离子免疫脂质体对胆囊癌的治疗作用。
Therapeutic effects of long-circulating miR-135a-containing cationic immunoliposomes against gallbladder carcinoma.
机构信息
Department of General Surgery, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
Department of General Surgery, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
出版信息
Sci Rep. 2017 Jul 20;7(1):5982. doi: 10.1038/s41598-017-06234-8.
Gallbladder carcinoma (GBC) is the most common malignant tumour in the biliary tract, but effective therapeutics are lacking. Based on our previous studies, miR-135a is a potential tool to inhibit GBC proliferation. In this study, we constructed miR-135a-loaded DSPE-PEG2000 liposomes modified with Anti-EGFR antibodies (Anti-EGFR-CIL-miR-135a). The results of an analysis of their physicochemical properties indicated the particle size of it was 222.0 ± 2.1 nm in diameter with an uptake efficiency of 86.5%. Next, the post-treatment biological behaviours of GBC, specifically, invasion, metastasis and apoptosis, were evaluated. miR-135a inhibited GBC invasion and metastasis and promoted apoptosis compared to controls. Additionally, miR-135a targeted and regulated the expression of ROCK1, HOXA10 and BCL-2. Due to the targeted effects of Anti-EGFR-CIL-miR-135a, the GBC tumour growth rate was 60% lower in an in vivo xenograft-bearing mouse model compared to controls. Thus, Anti-EGFR-CIL-miR-135a is a promising therapeutic strategy to combat GBC.
胆囊癌（GBC）是胆道系统最常见的恶性肿瘤，但缺乏有效的治疗方法。基于我们之前的研究，miR-135a 是一种潜在的抑制 GBC 增殖的工具。在本研究中，我们构建了装载 miR-135a 的 DSPE-PEG2000 脂质体，并用抗 EGFR 抗体（Anti-EGFR-CIL-miR-135a）进行了修饰。对其理化性质的分析结果表明，其粒径为 222.0±2.1nm，摄取效率为 86.5%。接下来，我们评估了 GBC 的治疗后生物学行为，特别是侵袭、转移和凋亡。与对照组相比，miR-135a 抑制了 GBC 的侵袭和转移，并促进了细胞凋亡。此外，miR-135a 靶向并调节了 ROCK1、HOXA10 和 BCL-2 的表达。由于 Anti-EGFR-CIL-miR-135a 的靶向作用，在体内异种移植荷瘤小鼠模型中，GBC 的肿瘤生长速度比对照组低 60%。因此，Anti-EGFR-CIL-miR-135a 是一种有前途的治疗 GBC 的策略。
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