| 摘要: |
| 目的 探讨c-FLIP反义寡核苷酸(c-FLIP ASODN)纳米粒(NP)对裸鼠体内人眼眶横纹肌肉瘤移植瘤生长的影响,评估纳米粒作为基因载体的可行性。方法 皮下种植法建立裸鼠人眼眶横纹肌肉瘤动物模型,瘤体内分别注射c-FLIP反义寡核苷酸纳米粒(ASODN NP组)、未包裹的c-FLIP反义寡核苷酸(ASODN组)及生理盐水(NS组),观察肿瘤体积、组织形态学改变；应用蛋白质印迹分析法及免疫组化染色检测各组肿瘤组织c-FLIP的表达情况；应用TUNEL细胞凋亡检测试剂盒检测肿瘤组织细胞凋亡情况。结果 与其他两组相比,ASODN NP组肿瘤的生长受到抑制;蛋白质印迹分析显示ASODN NP组和ASODN组的c-FLIP表达均较NS组减少(P<0.05)；免疫组化显示c-FLIP表达于胞质,ASODN NP组c-FLIP阳性细胞较其余两组减少(P<0.05)；ASODN NP组及ASODN组肿瘤组织凋亡细胞增多,ASODN NP组更加明显,NS组仅见个别细胞凋亡。 结论 c-FLIP ASODN NP可有效抑制人眼眶横纹肌肉瘤裸鼠移植瘤的生长。NP可作为一种安全有效的ASODN导入载体。 |
| 关键词: 反义寡核苷酸类 纳米粒子 c-FLIP 横纹肌肉瘤 裸小鼠 |
| DOI： |
| 投稿时间：2013-05-10修订日期：2013-06-30 |
| 基金项目:上海市科委纳米专项基金(0352nm114). |
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| c-FLIP antisense oligonucleotide-loaded nanoparticles inhibit growth of human orbital rhabdomyosarcoma xenograft in nude mice |
| LIANG Li1,WEI Rui-li2* |
(1. Department of Ophthalmology, Anhui Provincial Hospital, Hefei 230001, Anhui, China
2. Department of Ophthalmology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author.) |
| Abstract: |
| Objective To investigate the effect of cellular Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP) antisense oligonucleotide (ASODN)-loaded nanoparticles (NP) on the human orbital rhabdomyosarcoma xenograft in nude mice, so as to assess the feasibility of nanoparticles as a gene vector. Methods The model of human orbital rhabdomyosarcoma xenograft was established in nude mice, and the tumors were injected with c-FLIP ASODN NP, c-FLIP ASODN or normal saline (NS). The tumor volume and histopathological changes of tumor were observed. Western blotting analysis and immunohistochemical analysis were used to examine the expression of c-FLIP in tumor tissues of each group. Apoptosis of tumor cells was detected using TUNEL method. Results The growth of human orbital rhabdomyosarcoma in nude mice was significantly inhibited in ASODN NP group compared with the other two groups. Western blotting analysis showed that c-FLIP protein expression in ASODN NP and ASODN groups was significantly decreased compared with NS group (P<0.05). Immunohistochemical study showed that c-FLIP expression was found in the endochylema, and the c-FLIP positive cells in ASODN NP group was significantly less than those in the other two groups (P<0.05). Tumor cell apoptosis was observed in both ASODN NP and ASODN groups, with more found in the former, and only a few apoptotic cells were found in the NS group. Conclusion c-FLIP ASODN NP can effectively inhibit the growth of human orbital rhabdomyosarcoma xenograft in nude mice, indicating that nanoparticles may serve as a safe and effective vector for ASODN. |
| Key words: antisense oligonucleotides nanoparticles c-FLIP rhabdomyosarcoma nude mice |
