Tumor-penetrating peptide fused EGFR single-domain antibody enhances radiation responses following EGFR inhibition in gastric cancer
Tumor-penetrating peptide fused EGFR single-domain antibody enhances radiation responses following EGFR inhibition in gastric cancer
复制标题
肿瘤穿透肽融合 EGFR 单域抗体可增强胃癌中 EGFR 抑制后的放射反应。
DOI：
10.3892/or.2018.6532
复制
发表时间：
2018-09-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Baorui
中科院分区：
文献类型：
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作者：
Ji, Fuzhi;Sha, Huizi;Liu, Baorui
放疗已成为几种不可切除肿瘤（包括胃癌）局部控制的主要方法。胃癌患者经常表达高水平的表皮生长因子受体（EGFR），放疗后发现其增加。这为靶向EGFR的抗体与放疗的结合提供了基础。在我们前期的研究中，我们构建了一个具有双特异性靶点和高通透性的蛋白（anti-EGFR-iRGD），并研究了其对胃癌细胞增殖的抑制作用。在本研究中，研究了抗EGFR- irgd调节辐射反应的能力，并在显示高水平EGFR的胃癌细胞系和异种移植物中评估了这些相互作用的具体机制。抗EGFR- irgd的放射增强与抑制辐射诱导的EGFR上调、抑制细胞增殖和促进细胞凋亡有关。此外，抗egfr - irgd似乎在放疗后更多地渗透到肿瘤组织中。这些结果表明，抗egfr - irgd重组蛋白在egfr过表达的胃癌细胞和异种移植物中是一种选择性和有效的放射增敏剂。这些结果进一步表明，抗egfr - irgd是一种潜在的egfr靶向联合放疗的优越疗法。总的来说，本研究表明抗egfr - irgd可能是临床前和临床应用的有希望的候选药物。
Radiotherapy has been the primary method for the local control of several types of unresectable tumor, including gastric cancer. Patients with gastric cancer frequently express high levels of epidermal growth factor receptor (EGFR), which have been found to increase following radiotherapy treatment. This provides a basis for the combination of antibodies targeting EGFR and radiotherapy. In our previous study, a protein (anti-EGFR-iRGD) with bispecific targets and high permeability was constructed, and its effects on inhibiting the proliferation of gastric cancer cells was investigated. In the present study, the capacity of anti-EGFR-iRGD to modulate a radiation response was investigated and the specific mechanisms underlying these interactions were evaluated in gastric cancer cell lines and xenografts exhibiting high levels of EGFR. The radioenhancement of anti-EGFR-iRGD was associated with inhibited radiation-induced upregulation of EGFR, inhibited cell proliferation and promotion of cell apoptosis. In addition, anti-EGFR-iRGD appeared to permeate more into the tumor tissue following radiation. These findings indicated that the recombinant protein anti-EGFR-iRGD was a selective and effective radiosensitizer in EGFR-overexpressing gastric cancer cells and xenografts. These results further suggested that anti-EGFR-iRGD is a potential superior EGFR-targeted therapy combined with radiotherapy. Overall, the present study suggested that anti-EGFR-iRGD may be a promising candidate for preclinical and clinical use.