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

Sato, Shoki; Nakamura, Toru; Katagiri, Toyomasa et al.

Oncotarget, 2017, 8(69), 113662-113672

Permalink : https://hdl.handle.net/2115/68595

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論文情報

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アクセス権
open access
URI
https://hdl.handle.net/2115/68595
タイトル
Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation
著者
Sato, Shoki ; Nakamura, Toru ; Katagiri, Toyomasa ; Tsuchikawa, Takahiro ; Kushibiki, Toshihiro ; Hontani, Kouji ; Takahashi, Mizuna ; Inoko, Kazuho ; Takano, Hironobu ; Abe, Hirotake ; Takeuchi, Shintaro ; Ono, Masato ; Kuwabara, Shota ; Umemoto, Kazufumi ; Suzuki, Tomohiro ; Sato, Osamu ; Nakamura, Yusuke ; Hirano, Satoshi
著者名
Sato, Shoki
e-Rad_Researcher
70645796
著者名
Nakamura, Toru
著者名
Katagiri, Toyomasa
e-Rad_Researcher
50507572
著者名
Tsuchikawa, Takahiro
著者名
Kushibiki, Toshihiro
著者名
Hontani, Kouji
著者名
Takahashi, Mizuna
著者名
Inoko, Kazuho
著者名
Takano, Hironobu
著者名
Abe, Hirotake
著者名
Takeuchi, Shintaro
著者名
Ono, Masato
著者名
Kuwabara, Shota
著者名
Umemoto, Kazufumi
著者名
Suzuki, Tomohiro
著者名
Sato, Osamu
著者名
Nakamura, Yusuke
e-Rad_Researcher
50322813
著者名
Hirano, Satoshi
言語
英語
キーワード
C16orf74
pancreatic ductal adenocarcinoma
cell-permeable peptide
molecular target therapy
発行日
2017-12-26
出版者
Impact Journals
収録物名
Oncotarget
巻(号)
8(69)
ページ
113662-113672
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution 3.0 Unported
PISSN
1949-2553
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.18632/oncotarget.21939