Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells

被引：62

作者：

Li, Jiajin ^{[1
,2
]}

Yan, Hui ^{[1
,2
]}

Zhao, Li ^{[1
,2
]}

Jia, Wenzhi ^{[1
,2
]}

Yang, Hao ^{[3
,4
]}

Liu, Liu ^{[1
,2
]}

Zhou, Xiang ^{[1
,2
]}

Miao, Ping ^{[1
,2
]}

Sun, Xiaoguang ^{[1
,2
]}

Song, Shaoli ^{[1
,2
]}

Zhao, Xiaoping ^{[1
,2
]}

Liu, Jianjun ^{[1
,2
]}

Huang, Gang ^{[1
,2
,3
,4
,5
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Nucl Med, Shanghai 200127, Peoples R China

[2] Shanghai Jiao Tong Univ, Inst Clin Nucl Med, Sch Med, Ren Ji Hosp, Shanghai 200127, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai 200025, Peoples R China

[4] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200025, Peoples R China

[5] Shanghai Univ Med & Hlth Sci, Shanghai 201318, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 32期

基金：

中国国家自然科学基金;

关键词：

lung cancer; gefitinib; SREBP; chemotherapy; lipid metabolism; MEMBRANE-FLUIDITY; SMALL-MOLECULE; GROWTH; METABOLISM; ACTIVATION; EXPRESSION; RESISTANCE;

D O I：

10.18632/oncotarget.10721

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The clinical success of EGFR inhibitors in patients with lung cancer is limited by the inevitable development of treatment resistance. Here, we show that inhibition of SREBP increase gefitinib sensitivity in vitro and in vivo. Interference of SREBP1 binding partner MARVELD1 potentiate the therapeutic effect of gefitinib as well. Mechanistically, SREBP inhibition decreases the cell membrane fluidity, results in a decreased tyrosine phosphorylation of EGFR. Therefore, targeting lipid metabolism combined with EGFR-TKIs is potentially a novel therapeutic strategies for cancer treatment.

引用

收藏

页码：52392 / 52403

页数：12

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