天津医药

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纳米分子PAMAM作为miR药物载体靶向胃腺癌的功能研究

宋玮1,姜忠敏2,徐萍1,梁英虹1,刘晓智3   

  1. 1. 天津市第五中心医院药剂科
    2. 天津市第五中心医院病理科
    3. 天津市第五中心医院中心实验室
  • 收稿日期:2013-06-26 修回日期:2013-09-04 出版日期:2013-12-15 发布日期:2013-12-15
  • 通讯作者: 刘晓智

Function Study of the Nano-Molecular PAMAM as miR Carrier Targeting Gastric Adenocarcinoma

SONG Wei 1,JIANG Zhong min2,XU Ping 1,LIANG Ying hong1,LIU xiao zhi3   

  1. 1. Department of Pharmacy, The Fifth Central Hospital of Tianjin
    2. Department of Pathology,The Fifth Central Hospital of Tianjin
    3. The Central Laboratory,The Fifth Central Hospital of Tianjin
  • Received:2013-06-26 Revised:2013-09-04 Published:2013-12-15 Online:2013-12-15
  • Contact: LIU xiao zhi

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摘要：

【摘要】  目的  检测纳米级生物材料聚酰胺-胺（PAMAM）作为微小RNA（miR）基因投递载体对胃腺癌细胞的功能作用，为研发高效小分子靶向投递药物奠定基础。  方法  透析法制备叶酸（FA）/PAMAM络合物；分别以FA/PAMAM络合物和脂质体为载体转染miR-7至胃腺癌细胞株SGC-7901，荧光显微镜观察络合物转染效率，实时定量聚合酶链式反应（qRT-PCR）方法检测miR-7水平；细胞免疫荧光法检测miR-7靶基因表皮生长因子受体（EGFR）、蛋白激酶B（PKB）和细胞增殖活性抗原（PCNA）的表达；Transwell体系检测瘤细胞迁移能力。  结果  与脂质体相比较，FA/PAMAM络合物可显著提高SGC-7901细胞miR-7表达水平，降低瘤细胞EGFR、PKB和PCNA的水平，降低瘤细胞迁移百分率（均P＜0.05）。  结论  PAMAM可以作为小分子药物miR的靶向投递载体，有望进一步推动新的基因靶向药物研发。

关键词: 胃腺癌, 脂质体, 微小RNA, 纳米材料, 聚酰胺-胺

Abstract:

[Abstract]   Objective   To study the function of the nano-molecular polyamide-amine (PAMAM) as microRNA(miR)
carrier targeting gastric adenocarcinoma, and the foundation of developing an efficient delivery of small molecule drugs targeting gastric cancer thereof.  Methods   Thefolic acid (FA) /PAMAM comoles compound was prepared by dialysis method. After transfection of miR-7or liposomes into SGC-7901cell line, fluorescence microscope was used to detect the gene transfect efficiency. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the miR-7level. The immunocytochemistry assay was used to test the protein expressions of epidermal growth factor receptor (EGFR), protein kinase B (PKB) and proliferating cell nuclearantigen (PCNA). The transwell system was utilized to explore the migration ability of tumor cells.  Results   Compared with liposme, FA/PAMAN complex compound can significantly improve the level of miR-7 in SGC-7901cells，reduce the protein levels of EGFR, PKB and PCNA in SGC-7901cells, and also reduce the percentage of cancer cell migration (P＜0.05).   Conclusion   PAMAM can effectively transfect miR into gastric cancer cells, which is expected to become an efficient delivery of small molecule drugs.

Key words: gastric adenocarcinoma, liposomes, microRNA, nanomaterials, polyamide-amine