长期服用用于治疗非小细胞肺癌（NSCLC）的酪氨酸激酶抑制剂（TKI）会诱导细胞对 TKI 产生耐药性。耐药细胞的出现需要联合使用另一种治疗剂，并可能引起胃肠道和中枢神经系统的副作用。在之前的研究中，我们发现西仑吉肽的衍生物（一种环状精氨酸-甘氨酸-天冬氨酸（RGD）肽）具有非小细胞肺癌（NSCLC）细胞凋亡和抗上皮间质转化（EMT）作用。特别是，cRGDwV 和 cRGDyV 是含有芳香族氨基酸的环肽，被发现可以抑制 NSCLC 细胞生长、TGF-β1 诱导的 EMT 和侵袭。在这项研究中，我们证实了 cRGDwV 和 cRGDyV 对吉非替尼耐药 NSCLC A549 (A549GR) 细胞增殖、TGF-β1 诱导的 EMT 标志物表达、迁移和侵袭的影响。在A549GR细胞中，cRGDwV和cRGDyV对间充质标志物的表达、迁移和侵袭表现出抑制作用。这些结果表明，含有芳香族氨基酸的环状 RGD 肽可用于抑制吉非替尼耐药细胞中的间充质标志物表达以及迁移和侵袭。版权所有 © 2023 Seo、Seo 和 Kim。

Long-term administration of tyrosine kinase inhibitors (TKIs) used for the treatment of non-small cell lung cancer (NSCLC) induces TKI resistance in cells. The appearance of resistant cells requires the combined administration of another therapeutic agent and may cause side effects in the gastrointestinal and central nervous system. In previous studies, we found that derivatives of cilengitide, a cyclic Arg-Gly-Asp (RGD) peptide, exert NSCLC apoptotic and anti-epithelial-mesenchymal transition (EMT) effects. In particular, cRGDwV and cRGDyV, which are cyclic peptides containing aromatic amino acids, were found to inhibit NSCLC cell growth, TGF-β1-induced EMT, and invasion. In this study, we confirmed the effects of cRGDwV and cRGDyV on proliferation, TGF-β1-induced EMT marker expression, migration, and invasion in gefitinib-resistant NSCLC A549 (A549GR) cells. In A549GR cells, cRGDwV and cRGDyV showed inhibitory effects on the expression of mesenchymal marker expression, migration, and invasion. These results indicate that cyclic RGD peptides containing aromatic amino acids can be used to inhibit mesenchymal marker expression as well as migration and invasion in gefitinib-resistant cells.Copyright © 2023 Seo, Seo and Kim.