PUBLICATION
Zebrafish Xenograft Model of Human Lung Cancer for Evaluating Osimertinib Resistance
- Authors
- Li, X.Y., Huang, L.T., Wu, J.Q., He, M.F., Zhu, S.H., Zhan, P., Lv, T.F., Song, Y.
- ID
- ZDB-PUB-190729-3
- Date
- 2019
- Source
- BioMed Research International 2019: 3129748 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Acrylamides/pharmacology*
- Aniline Compounds/pharmacology*
- Animals
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Disease Models, Animal
- Drug Resistance, Neoplasm/drug effects
- ErbB Receptors/genetics*
- Gefitinib/adverse effects
- Gefitinib/pharmacology
- Humans
- Lung Neoplasms/drug therapy*
- Lung Neoplasms/genetics
- Lung Neoplasms/pathology
- Mutation
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Pathologic/genetics
- Neovascularization, Pathologic/pathology
- Protein Kinase Inhibitors/pharmacology
- Xenograft Model Antitumor Assays
- Zebrafish/genetics
- PubMed
- 31346515 Full text @ Biomed Res. Int.
Citation
Li, X.Y., Huang, L.T., Wu, J.Q., He, M.F., Zhu, S.H., Zhan, P., Lv, T.F., Song, Y. (2019) Zebrafish Xenograft Model of Human Lung Cancer for Evaluating Osimertinib Resistance. BioMed Research International. 2019:3129748.
Abstract
About half of NSCLC patients with EGFR mutation had secondary mutation T790M after treatment with a first-generation tyrosine kinase inhibitor (TKI), Gefitinib. The third-generation of EGFR-TKI Osimertinib is suitable for patients with EGFR mutation and T790M mutation. However, drug screening for NSCLC patients after the emergence of acquired resistance has become a difficult problem for clinicians. In this study, we established drug-resistant cell lines of Gefitinib and Osimertinib to evaluate cell proliferation in vitro. And we investigated the inhibitory effect of different drug concentration gradients on cancer cells. Zebrafish with high homology to human genes were selected as xenotransplantation models to compare the effects of different concentrations of Osimertinib on the proliferation and angiogenesis of zebrafish tumors after transplantation of different lung cancer cell lines. It was confirmed that Osimertinib could inhibit the proliferation of tumor cells with EGFR mutation and T790M resistance mutation in zebrafish, which was consistent with the clinical research conclusion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping