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10 April 2020 : Laboratory Research  

Inhibitor of Differentiation 1 (ID1) Facilitates the Efficacy of Sorafenib in Non-Small Cell Lung Cancer Cells through Suppressing Epithelial to Mesenchymal Transition

Yu-xiao Zhao1BDE, Jian Liu2ACF*

DOI: 10.12659/MSM.922148

Med Sci Monit 2020; 26:e922148


BACKGROUND: Sorafenib, which is a multitargeted kinase inhibitor, has shown some antitumor effects in patients with non-small cell lung cancer (NSCLC). However, the potential target of sorafenib’s antitumor activity is largely unknown. Moreover, definitive predictive biomarkers of benefit have rarely been reported.

MATERIAL AND METHODS: The alteration in inhibitor of differentiation 1 (ID1) expression in NSCLC cells with sorafenib treatment was detected by western blotting. The sensitivity of NSCLC cells to sorafenib was observed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. Loss-of-function and gain-of-function experiments were performed to observe the role of ID1 expression in epithelial to mesenchymal transition (EMT) progression.

RESULTS: Initially, we observed that ID1 was downregulated in NSCLC cells treated with sorafenib. The response of NSCLC cells to sorafenib was inhibited by the transfection of small interfering RNAs (siRNAs) targeting ID1. In contrast, the transfection of ID1-overexpressing plasmids improved the response of NSCLC cells to sorafenib. Further experiments indicated that ID1 is expressed at high levels in epithelial H460 cells and expressed at low levels in mesenchymal H358 cells. Loss-of-function and gain-of-function experiments suggested that ID1 negatively regulates EMT in NSCLC.

CONCLUSIONS: The expression of ID1 is dose-dependently inhibited by sorafenib, and the overexpression of ID1 contributes to the antitumor activity of sorafenib by suppressing EMT development. Our results indicate that ID1 might be a potential target for the antitumor activity of sorafenib in NSCLC and that targeting ID1 is a feasible strategy to improve the sensitivity of NSCLC cells to sorafenib.

Keywords: sorafenib, Inhibitor of Differentiation Protein 1, Physiological Effects of Drugs, Down-Regulation, Epithelial-mesenchymal transition, Gene Expression Regulation, Neoplastic, Protein Kinase Inhibitors, RNA Interference, RNA, Small Interfering



12 September 2022 : Editorial  

Editorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)

Ana Luisa Ordóñez-Vázquez, Sofía Murúa Beltrán-Gall, Shreya C. Pal, Nahum Méndez-Sánchez
Liver Research Unit, Medica Sur Clinic Foundation, Mexico City, Mexico

DOI: 10.12659/MSM.938365

Med Sci Monit 2022; 28:e938365


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750