Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice

Hironobu Takano, Toru Nakamura, Takahiro Tsuchikawa, Toshihiro Kushibiki, Kouji Hontani, Kazuho Inoko, Mizuna Takahashi, Shoki Sato, Hirotake Abe, Shintaro Takeuchi, Nagato Sato, Kei Hiraoka, Hiroshi Nishihara, Toshiaki Shichinohe, Satoshi Hirano

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)41063-41076
Number of pages14
JournalOncotarget
Volume6
Issue number38
DOIs
Publication statusPublished - 2015

Keywords

  • 2,5-dimethylpyrrolyl benzoic acid
  • EphA4
  • Human pancreatic cancer
  • Orthotopic models
  • Prognostic factor

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Takano, H., Nakamura, T., Tsuchikawa, T., Kushibiki, T., Hontani, K., Inoko, K., Takahashi, M., Sato, S., Abe, H., Takeuchi, S., Sato, N., Hiraoka, K., Nishihara, H., Shichinohe, T., & Hirano, S. (2015). Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice. Oncotarget, 6(38), 41063-41076. https://doi.org/10.18632/oncotarget.5729