Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
Department of General Surgery, The Central Hospital of Tongchuan Mining Bureau, Tongchuan, Shaanxi 727000, PR China.
Biomed Pharmacother. 2017 Sep;93:1136-1143. doi: 10.1016/j.biopha.2017.06.103. Epub 2017 Jul 19.
Gastric cancer is one of the most of common cancers in the world. 5-Fluorouracil (5-FU) has been identified as one of the standard first-line chemotherapy drugs for locally advanced or metastatic gastric cancer. However, poor tumor penetration, bad selectivity and toxic side effects are the major limitations for the application of chemotherapy drugs in anticancer therapy. Recently, plenty of studies demonstrate that the novel tumor-homing peptide iRGD could promote the tumor-penetrating capability of chemotherapy drugs in multiple cancers, and neuropilin-1 (NRP1) protein is the critical mediator for iRGD. Here,we found that NRP1 protein expression was significantly up-regulated in gastric cancer tissues and cell lines by Immunohistochemistry and Western blot. And elevated NRP1 was notably associated with tumor differentiation (P=0.021), tumor size (P=0.004), tumor stage(P=0.028), lymph node metastasis(P=0.032), TNM tumor stage (P=0.006) and poorer prognosis. Functionally, the data of Methyl thiazolyl tetrazolium (MTT) assay, Colony formation assay and Transwell assay revealed that NRP1 could facilitate gastric cancer cells proliferation, migration and invasion. Furthermore, iRGD could strengthen the chemotherapy effect of 5-FU on gastric cancer cells through NRP1. Taken together, NPR1 might be a promising tumor target for gastric cancer, and combination of iRGD with 5-FU may be a novel and valuable approach to improving the prognosis of gastric cancer patients.
胃癌是世界上最常见的癌症之一。5-氟尿嘧啶（5-FU）已被确定为局部晚期或转移性胃癌的标准一线化疗药物之一。然而，肿瘤穿透性差、选择性差和毒副作用大是化疗药物在抗癌治疗中的主要限制。最近，大量研究表明，新型肿瘤归巢肽 iRGD 可以促进多种癌症中化疗药物的肿瘤穿透能力，神经纤毛蛋白-1（NRP1）蛋白是 iRGD 的关键介导物。在这里，我们通过免疫组织化学和 Western blot 发现 NRP1 蛋白在胃癌组织和细胞系中表达显著上调。并且升高的 NRP1 与肿瘤分化（P=0.021）、肿瘤大小（P=0.004）、肿瘤分期（P=0.028）、淋巴结转移（P=0.032）、TNM 肿瘤分期（P=0.006）和预后不良显著相关。功能上，噻唑蓝（MTT）测定、集落形成测定和 Transwell 测定的数据表明，NRP1 可以促进胃癌细胞的增殖、迁移和侵袭。此外，iRGD 可以通过 NRP1 增强 5-FU 对胃癌细胞的化疗效果。综上所述，NRP1 可能是胃癌有前途的肿瘤靶点，iRGD 与 5-FU 的联合可能是改善胃癌患者预后的一种新的有价值的方法。
