Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice.
Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice.
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DOI：
10.18632/oncotarget.5729
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Hirano S
中科院分区：
文献类型：
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作者：
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
肝配蛋白受体A4（EphA4）在人胰腺癌（PDAC）中过表达并激活细胞生长。最近的研究已经确定了阻断EphA4的小分子。在这项研究中，我们研究了EphA4表达与PDAC患者预后之间的相关性。我们还检查了2，5_二甲基吡咯基苯甲酸（化合物1）（一种阻断EphA4的小分子）在PDAC细胞中的细胞抑制功效。EphA4阳性患者的总生存期显著短于EphA4阴性患者（P = 0.029）。多因素分析显示EphA4表达是PDAC患者的独立预后因素（P = 0.039）。化合物1在体外和体内表达EphA4的PDAC细胞中显示出细胞抑制功效。我们的研究表明，化合物1抑制EphA4和Akt磷酸化，并诱导表达EphA4的PDAC细胞凋亡。总之，化合物1具有作为PDAC患者的治疗剂的高潜力。
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.