| Title: | Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice |
| Authors: | Takano, Hironobu Browse this author |
| Nakamura, Toru Browse this author →KAKEN DB |
| Tsuchikawa, Takahiro Browse this author →KAKEN DB |
| Kushibiki, Toshihiro Browse this author |
| Hontani, Kouji Browse this author |
| Inoko, Kazuho Browse this author |
| Takahashi, Mizuna Browse this author |
| Sato, Shoki Browse this author |
| Abe, Hirotake Browse this author |
| Takeuchi, Shintaro Browse this author |
| Sato, Nagato Browse this author |
| Hiraoka, Kei Browse this author |
| Nishihara, Hiroshi Browse this author →KAKEN DB |
| Shichinohe, Toshiaki Browse this author →KAKEN DB |
| Hirano, Satoshi Browse this author →KAKEN DB |
| Keywords: | EphA4 |
| prognostic factor |
| 2,5-dimethylpyrrolyl benzoic acid |
| human pancreatic cancer |
| orthotopic models |
| Issue Date: | 19-Oct-2015 |
| Publisher: | Impact Journals |
| Journal Title: | Oncotarget |
| Volume: | 6 |
| Issue: | 38 |
| Start Page: | 41063 |
| End Page: | 41076 |
| Publisher DOI: | 10.18632/oncotarget.5729 |
| Abstract: | Ephrin receptor A4 (EphA4) is overexpressed in human pancreatic adenocarcinoma (PDAC) and activate cell growth. Recent studies have identified small molecules that block EphA4. In this study, we investigated the correlation between EphA4 expression and the prognosis of patients with PDAC. We also examined the cytostatic efficacy of 2,5-dimethylpyrrolyl benzoic acid (compound 1), a small molecule that blocks EphA4, in PDAC cells. Overall survival of patients with EphA4 positivity was significantly shorter than that of patients with EphA4 negativity (P = 0.029). In addition, multivariate analysis revealed that EphA4 expression was an independent prognostic factor in PDAC patients (P = 0.039). Compound 1 showed a cytostatic efficacy in PDAC cells expressing EphA4 in vitro and in vivo. Our study indicated that compound 1 suppressed both EphA4 and Akt phosphorylations, and induced apoptosis in PDAC cells expressing EphA4. In conclusion, compound 1 has a high potential as a therapeutic agent for patients with PDAC. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/60647 |
| 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)
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