ReferenceID 4958

Cucurbitacin D Overcomes Gefitinib Resistance by Blocking EGF Binding to EGFR and Inducing Cell Death in NSCLCs

Front Oncol

In this study, the mechanism of the anticancer effect through which cucurbitacin D (CuD) can overcome gefitinib resistance in NSCLC was investigated. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2-5-diphen

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Reference Id
4958
Evidence Id
21548
Core Evidence Id
21548
Source Reference Id
3246
Herb2 Reference Id
HBREF004043
Subject Paper Key
HBIN021848_32133284
Pubmed Id
32133284
Doi
10.3389/fonc.2020.00062
Paper Title
Cucurbitacin D Overcomes Gefitinib Resistance by Blocking EGF Binding to EGFR and Inducing Cell Death in NSCLCs
Paper Abstract
In this study, the mechanism of the anticancer effect through which cucurbitacin D (CuD) can overcome gefitinib resistance in NSCLC was investigated. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay, and cell migration and growth were observed by wound healing and colony formation assays, respectively. Levels of EGFR family members, protein kinase B, extracellular signal-regulated kinase, poly(ADP-ribose) polymerase, and G2/M phase-related proteins were detected by Western blot analysis. Immunofluorescence analysis was used to detect the intracellular expression of p-EGFR. Induction of apoptosis and cell cycle arrest was measured by flow cytometry. Solid-phase binding assays were used to determine binding to the EGFR family. CuD inhibits the phosphorylation of EGFR in gefitinib-resistant NSCLC cells and induces cell death via cell cycle arrest and apoptosis. CuD treatment or EGFR knockdown also suppressed the growth of gefitinib-resistant NSCLC cells. In addition, CuD overcame resistance by blocking EGF binding to EGFR in gefitinib-resistant NSCLC cells. In conclusion, we demonstrate that CuD overcomes gefitinib resistance by reducing the activation of EGFR-mediated survival in NSCLC and by inhibiting the combination of EGF and EGFR.
Journal
Front Oncol
Publish Year
2020
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Cucurbitacin D Overcomes Gefitinib Resistance by Blocking EGF Binding to EGFR and Inducing Cell Death in NSCLCs
Bilingual Status
semi_complete