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High cholesterol in lipid rafts reduces the sensitivity to EGFR‐TKI therapy in non‐small cell lung cancer
Author(s) -
Chen Qiufang,
Pan Zhenzhen,
Zhao Min,
Wang Qin,
Qiao Chen,
Miao Liyun,
Ding Xuansheng
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26351
Subject(s) - gefitinib , lung cancer , cholesterol , cancer research , lipid raft , medicine , oncology , epidermal growth factor receptor , chemistry , pharmacology , 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 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.