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

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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.

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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.

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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

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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

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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

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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