https://scholars.lib.ntu.edu.tw/handle/123456789/503595
標題: | Targeted Delivery of C/EBPα-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC | 作者: | Yoon S. KAI-WEN HUANG Andrikakou P. Vasconcelos D. Swiderski P. Reebye V. Sodergren M. Habib N. Rossi J.J. |
關鍵字: | adjuvant; advanced PDAC; albumin affinity tag; anti-tumor effects; C/EBPα-saRNA; clathrin-mediated endocytosis; targeted delivery; transferrin receptor aptamer; truncation | 公開日期: | 2019 | 出版社: | Cell Press | 卷: | 18 | 起(迄)頁: | 142-154 | 來源出版物: | Molecular Therapy - Nucleic Acids | 摘要: | Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies; it preferentially metastasizes to the liver and is the main cause of death from this disease. In previous studies, small activating RNA against CCAAT/enhancer-binding protein-α (C/EBPα-saRNA) demonstrated efficacy of PDAC in a local subcutaneous tumor model. In this study, we focused on the efficacy of C/EBPα-saRNA in advanced stage PDAC. For targeted delivery, we selected a new anti-transferrin receptor aptamer (TR14), which demonstrated a high binding affinity to target proteins. The TR14 aptamer was internalized with clathrin-mediated endocytosis, distributed in early endosome, late endosome, and lysosome subcellularly. To investigate its anti-tumor effects to advanced PDAC, we conjugated C/EBPα-saRNA to TR14. Treatment of pancreatic cancer cells with the conjugates upregulated expression of C/EBPα and its downstream target p21, and inhibited cell proliferation. For in vivo assays, we established an advanced PDAC mouse model by engrafting luciferase reporter-PANC-1 cells directly into the livers of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After treatment of aptamer-C/EBPα conjugates, we observed significant reduction of tumor growth in this advanced PDAC mouse model. Combinational treatment of the conjugates with gemcitabine also demonstrated enhanced anti-tumor effects in advanced PDAC. This suggests that aptamer-C/EBPα conjugates could be used as an adjuvant, along with other conventional anti-cancer drugs in advanced PDAC. In conclusion, targeted delivery of C/EBPα-saRNAs by aptamers might have potential therapeutic effects in advanced PDAC. ? 2019 The Authors |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072279341&doi=10.1016%2fj.omtn.2019.08.017&partnerID=40&md5=96f05010beae5b5281284e7021697198 https://scholars.lib.ntu.edu.tw/handle/123456789/503595 |
ISSN: | 2162-2531 | DOI: | 10.1016/j.omtn.2019.08.017 | SDG/關鍵字: | aptamer; CCAAT enhancer binding protein alpha; clathrin; gemcitabine; protein p21; RNA; small activating RNA; tr14 aptamer; unclassified drug; advanced cancer; animal experiment; animal model; animal tissue; antineoplastic activity; Article; cancer inhibition; controlled study; drug efficacy; endocytosis; endosome; female; human; human cell; in vitro study; in vivo study; lysosome; mouse; nonhuman; pancreas adenocarcinoma; priority journal; protein expression; upregulation |
顯示於: | 醫學系 |
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