Effects of cilengitide derivatives on TGF-β1-induced epithelial-to-mesenchymal transition and invasion in gefitinib-resistant non-small cell lung cancer cells

Frontiers in Pharmacology

Pharmacology

Yujin Seo¹  Minji Seo¹  Jiyeon Kim² 

[1] Department of Biomedical Laboratory Science, School of Health Science, Dankook University, Cheonan, Republic of Korea;null;

关键词: Cilengitide;    cRGDwV;    cRGDyV;    EMT;    NSCLC;    A549GR;   

DOI  :  10.3389/fphar.2023.1277199

 received in 2023-08-14, accepted in 2023-09-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Seo, Seo and Kim.