| 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)
|
