High cholesterol in lipid rafts reduces the sensitivity to EGFR‐TKI therapy in non‐small cell lung cancer

Overcoming EGFR‐TKI resistant which has the initial enthusiasm over substantial clinical responses is a formidable challenge on nowadays. In this study, we showed that cholesterol level in lipid rafts in gefitinib resistant non‐small cell lung cancer (NSCLC) cell lines was remarkably higher than gef...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular physiology 2018-09, Vol.233 (9), p.6722-6732
Main Authors: Chen, Qiufang, Pan, Zhenzhen, Zhao, Min, Wang, Qin, Qiao, Chen, Miao, Liyun, Ding, Xuansheng
Format: Article
Language:English
Subjects:
AKT protein
Biotechnology
Cancer
Cholesterol
Depletion
drug resistant
Epidermal growth factor receptors
Gefitinib
Lipid rafts
Lung cancer
Non-small cell lung carcinoma
non‐small cell lung cancer
Phosphorylation
Rafts
Sensitivity enhancement
Tumor cell lines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Overcoming EGFR‐TKI resistant which has the initial enthusiasm over substantial clinical responses is a formidable challenge on nowadays. In this study, we showed that cholesterol level in lipid rafts in gefitinib resistant non‐small cell lung cancer (NSCLC) cell lines was remarkably higher than gefitinib sensitive cell line, and depletion of cholesterol increased gefitinib sensitivity. Furthermore, cholesterol‐depleted enhanced gefitinib inhibit phosphorylation of EGFR, Akt‐1, MEK1/2, and ERK1/2 and these were reversed in cholesterol add‐back experiments. Gefitinib resistant cell lines showed high affinity of gefitinib and EGFR when cholesterol was depleted. Therefore, targeting cholesterol combined with EGFR‐TKI is potentially a novel therapeutic strategy for gefitinib resistant treatment. Cholesterol level in lipid rafts in gefitinib resistant non‐small cell lung cancer (NSCLC) cell lines was remarkably higher than gefitinib sensitive cell line, and depletion of cholesterol increase gefitinib sensitivity. Furthermore, cholesterol‐depleted enhanced gefitinib inhibit phosphorylation of EGFR, Akt‐1, MEK1/2, and ERK1/2 and these were reversed in cholesterol add‐back experiments. Gefitinib resistant cell lines showed high affinity of gefitinib and EGFR when cholesterol was depleted. Therefore, targeting cholesterol combined with EGFR‐TKI is potentially a novel therapeutic strategy for gefitinib resistant treatment.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.26351