基因miRNA-34a靶向纳米复合物抗前列腺癌细胞增殖的作用研究

于淼; 毛峻琴

doi:10.3969/j.issn.1006-0111.2015.06.016

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名

邮箱

手机号码

标题

留言内容

验证码

基因miRNA-34a靶向纳米复合物抗前列腺癌细胞增殖的作用研究

doi: 10.3969/j.issn.1006-0111.2015.06.016

于淼,
毛峻琴

解放军85医院药剂科, 上海 200052

Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines

YU Miao,
MAO Junqin

Department of Pharmacy, No. 85 Hospital of PLA, Shanghai 200052, China

摘要: 目的通过构建具有前列腺癌细胞特异性靶向作用的基因载体适配体——聚乙二醇-聚酰胺-胺(APT-PEG-PAMAM),携带具有抗前列腺癌增殖作用的基因miRNA-34a,考察载体系统的转染效率及其对前列腺癌细胞的抑制作用。方法运用核磁共振(NMR)鉴定APT-PEG-PAMAM基因载体的结构;利用粒径电位仪对APT-PEG-PAMAM/miRNA纳米复合物进行表征;利用基因转染实验考察APT-PEG-PAMAM/miRNA纳米复合物在前列腺癌细胞(PC3和LNCaP)上的表达效果;利用CCK-8细胞增殖抑制实验考察APT-PEG-PAMAM/miRNA-34a对前列腺癌细胞的抑制作用。结果通过结构鉴定确定APT-PEG-PAMAM合成成功。定性、定量转染效率实验证明,经APT进一步修饰后,对LNCaP细胞转染效率显著增加,证明APT的靶向作用。CCK-8细胞增殖实验证明,APT-PEG-PAMAM/miRNA-34a对前列腺癌细胞具有抑制作用。结论 APT-PEG-PAMAM/miRNA-34a有望成为今后靶向治疗前列腺癌的基因药物。
- 微RNA /
- 聚酰胺-胺 /
- 靶向治疗 /
- 前列腺癌 /
- 基因载体
Abstract: Objective To construct a gene delivery carrier with aptamer-polyethylene glycol-dendrimer-polyamidoamine (APT-PEG-PAMAM), forming nanoparticles to specifically target prostate cancer cell lines, carrying prostate cancer cell proliferative suppressor microRNA: miRNA-34a. We investigated the transfection efficiency of this gene delivery system as well as functionally studied its inhibitory effect on prostate cancer (PCa) cell proliferation. Methods The construction of APT-PEG-PAMAM gene carrier was identified and confirmed by nuclear magnetic resonance (NMR). The nano-complex sizes and zeta potential of APT-PEG-PAMAM gene carrier complexes were measured by zeta sizer. The efficiency of gene transfection of APT-PEG-PAMAM / miRNA nano-complexes were investigated by measuring the expression miRNA-34a in prostate cancer cells (PC3 and LNCaP);the PCa specific cell proliferation inhibition of APT-PEG-PAMAM / miRNA-34a nano-complexes were investigated by measuring CCK-8 cell proliferation inhibition experiments by comparing with APT-PEG-PAMAM and APT-PEG-PAMAM / miRNA-34a nano-complexes. Results NMR Results demonstrated that APT-PEG-PAMAM / miRNA-34a nano-complexes were successfully synthesized by structural identification. Qualitative and quantitative transfection efficiency experiments data show that the cellular uptake of vectors were concentration-dependent, after the APT further modified it significantly and increased the LNCaP cell transfection efficiency and specificity of PCa cells targeting ability. CCK8 cell proliferation assay data indicated that APT-PEG-PAMAM/miRNA-34a has the anti-PCa cells effect. Conclusion APT-PEG-PAMAM/miRNA-34a may prove to see its efficacy for near future in pre-clinical and clinical study on the treatment of PCa.
- microRNA /
- polyamidoamine /
- cancer targeting /
- prostatic cancer /
- gene vector

[1]	陈万青,郑荣寿,曾红梅,等. 2011年中国恶性肿瘤发病和死亡分析[J]. 中国肿瘤,2015,24(1):1-10.
[2]	韩苏军,张思维,陈万青,等. 中国前列腺癌发病现状和流行趋势分析[J]. 临床肿瘤学杂志,2013,18(4):330-334.
[3]	Siegel R, Ma J, Zou Z, et al. Cancer statistics[J]. CA Cancer J Clin,2014,64(1):9-29.
[4]	Khraiwesh B, Arif MA, Seumel GI,et al. Transcriptional control of gene expression by microRNAs[J]. Cell, 2010, 140(1):111-122.
[5]	Gong MC, Chang SS, Sadelain M, et al. Prostate specific membrane antigen (PSMA)-specific monoclonal antibodies in the treatment of prostate and other cancers[J]. Cancer Metastasis Rev, 1999, 18:483 490.
[6]	Nery AA, Wrenger C, Ulrich H. Recognition of biomarkers and cell-specific molecular signatures: aptamers as capture agents[J]. J Sep Sci,2009, 32(10):1523-1530.
[7]	武鑫,蔡溱,朱全刚,等. YPSMA-1单克隆抗体修饰的树突状高分子前列腺癌靶向基因递送载体[J]. 中国药学杂志,2012,47(6):418-422.
[8]	Wu X, Ding B, Gao J, et al. Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy[J]. Int J Nanomedicine,2011, 6:1747-1756.
[9]	Hinson DL, Webber RJ. Miniaturization of the BCA protein assay[J]. Biotechniques,1988, 6(1):14-19.

[1]	李锐, 张倩倩, 王瑞冬, 高小峰. 国家集中带量采购政策下样本医院良性前列腺增生治疗药物使用情况分析 . 药学实践与服务, 2025, 43(2): 1-6. doi: 10.12206/j.issn.2097-2024.202408031
[2]	刘丽艳, 余小翠, 孙传铎. 纳武利尤单抗治疗非小细胞肺癌有效性及安全性的Meta分析 . 药学实践与服务, 2024, 42(10): 451-456. doi: 10.12206/j.issn.2097-2024.202310044
[3]	迟文雅, 袁艳, 李伟林, 吴茼妤, 俞媛. 负载骨髓间充质干细胞/白藜芦醇脂质体的水凝胶支架用于创伤性脑损伤治疗 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202406034
[4]	宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅. 帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
[5]	丁华敏, 郭羽晨, 秦春霞, 宋志兵, 孙莉莉. 消风止痒颗粒通过降低白三烯水平对小鼠特应性皮炎急性瘙痒的治疗作用研究 . 药学实践与服务, 2024, 42(5): 211-216. doi: 10.12206/j.issn.2097-2024.202306031
[6]	陈春娟, 郑志新, 李骊. 平喘方联合孟鲁司特钠治疗儿童支气管哮喘患者的临床疗效观察 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202405035
[7]	唐淑慧, 凤美娟, 薛智霞, 鲁桂华. 帕博利珠单抗治疗所致免疫相关不良反应与中医体质的相关性研究 . 药学实践与服务, 2024, 42(5): 217-222. doi: 10.12206/j.issn.2097-2024.202311029
[8]	景凯, 杨慈荣, 张圳, 臧艺蓓, 刘霞. 黄芪甲苷衍生物治疗慢性心力衰竭小鼠的药效评价及作用机制研究 . 药学实践与服务, 2024, 42(5): 190-197. doi: 10.12206/j.issn.2097-2024.202310004
[9]	孙丹倪, 黄勇, 张嘉宝, 王培. 代谢相关脂肪性肝病的无创诊断与药物治疗 . 药学实践与服务, 2024, 42(10): 411-418. doi: 10.12206/j.issn.2097-2024.202403049
[10]	张晶晶, 索丽娜, 郑兆红. 89例细菌性肝脓肿的临床特征及抗感染治疗分析 . 药学实践与服务, 2024, 42(6): 267-272. doi: 10.12206/j.issn.2097-2024.202302039
[11]	石晓萍, 吕迁洲, 李晓宇, 许青. 泊沙康唑对比伏立康唑经验治疗或诊断驱动治疗免疫功能低下患者侵袭性霉菌病的成本-效果分析 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202401050
[12]	陈莹, 许子华, 胡北, 崔亚玲, 高欢, 吴琼. 通便灵胶囊治疗便秘的药效与机制研究 . 药学实践与服务, 2024, 42(): 1-7. doi: 10.12206/j.issn.2097-2024.202404008
[13]	冯志惠, 邓仪卿, 叶冰, 安培, 张宏, 张海军. 雀梅藤石油醚提取物诱导三阴性乳腺癌细胞凋亡的实验研究 . 药学实践与服务, 2024, 42(6): 253-259. doi: 10.12206/j.issn.2097-2024.202311055
[14]	桂明珠, 李静, 李志玲. 儿童伏立康唑的血药浓度与CYP2C19、CYP2C9和CYP3A5基因多态性的相关性研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402020
[15]	宋泽成, 陈林林, 鲁仁义, 刘梦肖, 王彦. 脓毒症治疗的研究进展 . 药学实践与服务, 2024, 42(11): 457-460, 502. doi: 10.12206/j.issn.2097-2024.202405059
[16]	黄韵, 张正银, 金英, 郑怡菁, 李铁军, 孙莉莉. 耐碳青霉烯类肺炎克雷伯菌及大肠埃希菌临床分离株耐药性及耐药基因分析 . 药学实践与服务, 2024, 42(10): 439-444. doi: 10.12206/j.issn.2097-2024.202309059
[17]	王雪莲, 郑斯莉, 李志勇, 罗亨宇, 缪朝玉. 全身过表达人METRNL基因小鼠模型的构建与验证 . 药学实践与服务, 2024, 42(5): 198-202, 222. doi: 10.12206/j.issn.2097-2024.202311014
[18]	姚瑞阳, 于海征, 李耀盺, 张磊. 丹参FBXL 基因家族的鉴定和表达模式分析 . 药学实践与服务, 2024, 42(11): 461-470. doi: 10.12206/j.issn.2097-2024.202407034
[19]	张莲卿, 骆岩, 杨提, 姚佳晨, 李文艳. 基于FAERS数据库的艾塞那肽微球不良事件信号挖掘与研究 . 药学实践与服务, 2024, 42(10): 445-450. doi: 10.12206/j.issn.2097-2024.202403057
[20]	马兹芬, 许维恒, 金煜翔, 薛磊. 食管癌的靶向治疗与免疫治疗研究进展 . 药学实践与服务, 2024, 42(6): 231-237. doi: 10.12206/j.issn.2097-2024.202306008

点击查看大图

计量

文章访问数: 3015
HTML全文浏览量: 224
PDF下载量: 328
被引次数: 0

基因miRNA-34a靶向纳米复合物抗前列腺癌细胞增殖的作用研究

解放军85医院药剂科, 上海 200052

收稿日期: 2014-12-16

修回日期: 2015-04-23

关键词:

微RNA /

摘要: 目的通过构建具有前列腺癌细胞特异性靶向作用的基因载体适配体——聚乙二醇-聚酰胺-胺(APT-PEG-PAMAM),携带具有抗前列腺癌增殖作用的基因miRNA-34a,考察载体系统的转染效率及其对前列腺癌细胞的抑制作用。方法运用核磁共振(NMR)鉴定APT-PEG-PAMAM基因载体的结构;利用粒径电位仪对APT-PEG-PAMAM/miRNA纳米复合物进行表征;利用基因转染实验考察APT-PEG-PAMAM/miRNA纳米复合物在前列腺癌细胞(PC3和LNCaP)上的表达效果;利用CCK-8细胞增殖抑制实验考察APT-PEG-PAMAM/miRNA-34a对前列腺癌细胞的抑制作用。结果通过结构鉴定确定APT-PEG-PAMAM合成成功。定性、定量转染效率实验证明,经APT进一步修饰后,对LNCaP细胞转染效率显著增加,证明APT的靶向作用。CCK-8细胞增殖实验证明,APT-PEG-PAMAM/miRNA-34a对前列腺癌细胞具有抑制作用。结论 APT-PEG-PAMAM/miRNA-34a有望成为今后靶向治疗前列腺癌的基因药物。

Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines

Department of Pharmacy, No. 85 Hospital of PLA, Shanghai 200052, China

Received Date: 2014-12-16

Rev Recd Date: 2015-04-23

Keywords:

Abstract: Objective To construct a gene delivery carrier with aptamer-polyethylene glycol-dendrimer-polyamidoamine (APT-PEG-PAMAM), forming nanoparticles to specifically target prostate cancer cell lines, carrying prostate cancer cell proliferative suppressor microRNA: miRNA-34a. We investigated the transfection efficiency of this gene delivery system as well as functionally studied its inhibitory effect on prostate cancer (PCa) cell proliferation. Methods The construction of APT-PEG-PAMAM gene carrier was identified and confirmed by nuclear magnetic resonance (NMR). The nano-complex sizes and zeta potential of APT-PEG-PAMAM gene carrier complexes were measured by zeta sizer. The efficiency of gene transfection of APT-PEG-PAMAM / miRNA nano-complexes were investigated by measuring the expression miRNA-34a in prostate cancer cells (PC3 and LNCaP);the PCa specific cell proliferation inhibition of APT-PEG-PAMAM / miRNA-34a nano-complexes were investigated by measuring CCK-8 cell proliferation inhibition experiments by comparing with APT-PEG-PAMAM and APT-PEG-PAMAM / miRNA-34a nano-complexes. Results NMR Results demonstrated that APT-PEG-PAMAM / miRNA-34a nano-complexes were successfully synthesized by structural identification. Qualitative and quantitative transfection efficiency experiments data show that the cellular uptake of vectors were concentration-dependent, after the APT further modified it significantly and increased the LNCaP cell transfection efficiency and specificity of PCa cells targeting ability. CCK8 cell proliferation assay data indicated that APT-PEG-PAMAM/miRNA-34a has the anti-PCa cells effect. Conclusion APT-PEG-PAMAM/miRNA-34a may prove to see its efficacy for near future in pre-clinical and clinical study on the treatment of PCa.

全文HTML

参考文献 (9)

留言板

基因miRNA-34a靶向纳米复合物抗前列腺癌细胞增殖的作用研究

doi: 10.3969/j.issn.1006-0111.2015.06.016

Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines

计量

基因miRNA-34a靶向纳米复合物抗前列腺癌细胞增殖的作用研究

doi: 10.3969/j.issn.1006-0111.2015.06.016

解放军85医院药剂科, 上海 200052

English Abstract

Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines

Department of Pharmacy, No. 85 Hospital of PLA, Shanghai 200052, China

全文HTML

目录

留言板

基因miRNA-34a靶向纳米复合物抗前列腺癌细胞增殖的作用研究

doi: 10.3969/j.issn.1006-0111.2015.06.016

Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines

计量

出版历程

基因miRNA-34a靶向纳米复合物抗前列腺癌细胞增殖的作用研究

doi: 10.3969/j.issn.1006-0111.2015.06.016

解放军85医院药剂科, 上海 200052

English Abstract

Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines

Department of Pharmacy, No. 85 Hospital of PLA, Shanghai 200052, China

全文HTML

目录