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Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation

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Title: Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation
Authors: Sato, Shoki Browse this author
Nakamura, Toru Browse this author →KAKEN DB
Katagiri, Toyomasa Browse this author
Tsuchikawa, Takahiro Browse this author →KAKEN DB
Kushibiki, Toshihiro Browse this author
Hontani, Kouji Browse this author
Takahashi, Mizuna Browse this author
Inoko, Kazuho Browse this author
Takano, Hironobu Browse this author
Abe, Hirotake Browse this author
Takeuchi, Shintaro Browse this author
Ono, Masato Browse this author
Kuwabara, Shota Browse this author
Umemoto, Kazufumi Browse this author
Suzuki, Tomohiro Browse this author
Sato, Osamu Browse this author
Nakamura, Yusuke Browse this author
Hirano, Satoshi Browse this author →KAKEN DB
Keywords: C16orf74
pancreatic ductal adenocarcinoma
cell-permeable peptide
molecular target therapy
Issue Date: 26-Dec-2017
Publisher: Impact Journals
Journal Title: Oncotarget
Volume: 8
Issue: 69
Start Page: 113662
End Page: 113672
Publisher DOI: 10.18632/oncotarget.21939
Abstract: Background: Chromosome 16 open reading frame 74 (C16orf74) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell proliferation and invasion through binding to calcineurin (CN). Therefore, C16orf74 is a good target for the development of a PDAC treatment. A cell-permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN interaction was designed to examine whether this peptide can inhibit PDAC cell proliferation in vitro and in vivo. Method: TheDN-C16orf74 peptide, which corresponds to the portion of C16orf74 that interacts with CN, was synthesized, and we assessed its anti-tumor activity in proliferation assays with human PDAC cells and the underlying molecular signaling pathway. Using an orthotopic xenograft model of PDAC, we treated mice intraperitoneally with phosphate-buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor-suppressive effects. Result: DN-C16orf74 inhibited the binding of C16orf74 to CN in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation, and the level of suppression depended on the expression levels of C16orf74 in vitro. DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft model. Furthermore, the tumor-suppressive effect was associated with inhibition of the phosphorylation of Akt and mTOR. Conclusion: The cell-permeable peptide DN-C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/68595
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 中村 透

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