@Article{or.2026.081088,
AUTHOR = {Chi-Hsuan Wei, Pei-Yu Lin, Chia-Wei Weng, Meng-Fang Tsai, Jeremy J. W. Chen},
TITLE = {Synergistic Antitumour Effects of Harringtonine and Cresatin against Non-Small Cell Lung Cancer <i>In Vitro</i> and <i>In Vivo</i>},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/28029},
ISSN = {1555-3906},
ABSTRACT = {<b>Objectives:</b> Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths, largely due to late diagnosis, frequent metastasis, and acquired resistance to tyrosine kinase inhibitors (TKIs). Upregulation of epidermal growth factor receptor (EGFR) and Src promotes tumour progression, highlighting them as potential therapeutic targets. This study aims to investigate novel strategies to overcome tyrosine kinase inhibitor (TKI) resistance and improve NSCLC treatment outcomes. <b>Methods:</b> In this study, harringtonine and cresatin were identified using a previously established pharmacophore model and an enzyme-linked immunosorbent assay (ELISA)-based screening approach, respectively. NSCLC cell lines harbouring different EGFR genotypes were used to evaluate the inhibitory effects of harringtonine and cresatin on cell proliferation, migration, and invasion. Furthermore, <i>in vitro</i> assays and xenograft animal models were employed to validate the therapeutic potential of the combination treatment. <b>Results:</b> <i>In vitro</i> experiments demonstrated that both harringtonine and cresatin significantly reduced cell viability, proliferation, invasion, migration, and colony formation across NSCLC cell lines harbouring various EGFR genotypes. Treatment with harringtonine or cresatin also decreased the expression of EGFR- and Src-related signalling proteins. Notably, harringtonine and cresatin altered the phenotype of drug-resistant H1975 cells by reducing the activity of Rho GTPase proteins. Moreover, the combination of harringtonine and cresatin not only resulted in a lower dose but also synergistically inhibited tumour growth <i>in vivo</i> by suppressing the activity of the EGFR- and Src-associated pathways. <b>Conclusion:</b> Our findings highlight the use of harringtonine and cresatin as promising agents for the clinical treatment of NSCLC and offer new insights into drug repurposing strategies.},
DOI = {10.32604/or.2026.081088}
}