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

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

タイトル	en Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation
作成者	en Sato, Shoki en Nakamura, Toru NRID 1000070645796 en Katagiri, Toyomasa en Tsuchikawa, Takahiro NRID 1000050507572 en Kushibiki, Toshihiro en Hontani, Kouji en Takahashi, Mizuna en Inoko, Kazuho en Takano, Hironobu en Abe, Hirotake en Takeuchi, Shintaro en Ono, Masato en Kuwabara, Shota en Umemoto, Kazufumi en Suzuki, Tomohiro en Sato, Osamu en Nakamura, Yusuke en Hirano, Satoshi NRID 1000050322813
アクセス権	open access
権利情報	http://creativecommons.org/licenses/by/3.0/ en Creative Commons Attribution 3.0 Unported
主題	Other en C16orf74 Other en pancreatic ductal adenocarcinoma Other en cell-permeable peptide Other en molecular target therapy NDC 490
内容注記	Abstract en 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.
出版者	en Impact Journals
日付	Issued2017-12-26
言語	eng
資源タイプ	journal article
出版タイプ	VoR
資源識別子	HDL http://hdl.handle.net/2115/68595
関連	isIdenticalTo DOI https://doi.org/10.18632/oncotarget.21939
収録誌情報	PISSN 1949-2553 en Oncotarget 巻8 号69 開始ページ113662 終了ページ113672
ファイル	fulltext 21939-311592-3-PB.pdf 2.64 MB (application/pdf) Issued2017-12-26 fulltext 21939-311598-2-SP.pdf 1.63 MB (application/pdf) Issued2017-12-26
コンテンツ更新日時	2023-07-26