Zhang Yafei, Dou Xiaofeng, Yan Jianghua, Yang Rongshui, Su Xinhui
Department of Nuclear Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China.
Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, 201 Hubin South Road, Xiamen, 361004, China.
Discov Oncol. 2025 Jul 29;16(1):1437. doi: 10.1007/s12672-025-03149-z.
As a co-receptor for vascular endothelial growth factor, neuropilin receptor type-1 (NRP-1) plays a crucial role in tumor angiogenesis, growth, and metastasis, and is regarded as a promising target for cancer molecular imaging and therapy. However, few data on inhibitory effect of an anti-NRP-1 monoclonal antibody on HCC with different NRP-1 expression levels have been reported. This study aimed to investigate inhibitory effect of an anti-NRP-1 monoclonal antibody (A6-11-26) on different types of HCC, with a view to further understanding the role of A6-11-26 in HCC. Three different types of HCC cell lines (Bel-7402, SMMC-7721 and HepG2) were conducted in this study. MTT, colony formation test, cell morphology, and flow cytometry were used to assess the inhibitory effect of A6-11-26 on three HCC cell lines. The in vivo growth inhibitory effect of A6-11-26 was evaluated in mice xenograft models bearing three HCC cell lines respectively. Immunohistochemistry analyses was performed to characterize the expressions of vascular endothelial growth factor receptor (VEGFR) and NRP-1 in HCC tissues after A6-11-26 administration. A6-11-26 displayed to inhibit the proliferation, migration and apoptosis of HCC cells in vitro and tumor growth in vivo. The inhibitory effect of A6-11-26 was dose-dependent and dependent on the level of NRP-1 expression. The decreasing expressions of VEGFR and NRP-1 in HCC tissues after A6-11-26 treatment had also dose-dependent and NRP-1 expression characteristics. Taken together, an anti-NRP-1 monoclonal antibody (A6-11-26) can inhibit HCC growth through decreasing NRP-1 and VEGFR expression accordingly with NRP-1 expression characteristics, suggesting that A6-11-26 may be a potential targeted medicine for HCC with high NRP-1 expression.
作为血管内皮生长因子的共受体，1型神经纤毛蛋白受体（NRP-1）在肿瘤血管生成、生长和转移中起关键作用，被视为癌症分子成像和治疗的一个有前景的靶点。然而，关于抗NRP-1单克隆抗体对不同NRP-1表达水平的肝癌的抑制作用的数据报道较少。本研究旨在探讨抗NRP-1单克隆抗体（A6-11-26）对不同类型肝癌的抑制作用，以期进一步了解A6-11-26在肝癌中的作用。本研究采用了三种不同类型的肝癌细胞系（Bel-7402、SMMC-7721和HepG2）。采用MTT法、集落形成试验、细胞形态学观察和流式细胞术评估A6-11-26对三种肝癌细胞系的抑制作用。分别在携带三种肝癌细胞系的小鼠异种移植模型中评估A6-11-26的体内生长抑制作用。给药A6-11-26后，采用免疫组织化学分析来表征肝癌组织中血管内皮生长因子受体（VEGFR）和NRP-1的表达。A6-11-26在体外显示出抑制肝癌细胞的增殖、迁移和凋亡以及体内肿瘤生长的作用。A6-11-26的抑制作用呈剂量依赖性且依赖于NRP-1表达水平。A6-11-26治疗后肝癌组织中VEGFR和NRP-1表达的降低也具有剂量依赖性和NRP-1表达特征。综上所述，抗NRP-1单克隆抗体（A6-11-26）可通过相应降低NRP-1和VEGFR表达并具有NRP-1表达特征来抑制肝癌生长，表明A6-11-26可能是一种针对高NRP-1表达肝癌的潜在靶向药物。
