TY - JOUR
T1 - Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice
AU - Takano, Hironobu
AU - Nakamura, Toru
AU - Tsuchikawa, Takahiro
AU - Kushibiki, Toshihiro
AU - Hontani, Kouji
AU - Inoko, Kazuho
AU - Takahashi, Mizuna
AU - Sato, Shoki
AU - Abe, Hirotake
AU - Takeuchi, Shintaro
AU - Sato, Nagato
AU - Hiraoka, Kei
AU - Nishihara, Hiroshi
AU - Shichinohe, Toshiaki
AU - Hirano, Satoshi
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - 2,5-dimethylpyrrolyl benzoic acid
KW - EphA4
KW - Human pancreatic cancer
KW - Orthotopic models
KW - Prognostic factor
UR - http://www.scopus.com/inward/record.url?scp=84951174360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951174360&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.5729
DO - 10.18632/oncotarget.5729
M3 - Article
C2 - 26516928
AN - SCOPUS:84951174360
SN - 1949-2553
VL - 6
SP - 41063
EP - 41076
JO - Oncotarget
JF - Oncotarget
IS - 38
ER -
