Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells
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Jiajin Li1,2,*, Hui Yan1,2,*, Li Zhao1,2, Wenzhi Jia1,2, Hao Yang3, Liu Liu1,2, Xiang Zhou1,2, Ping Miao1,2, Xiaoguang Sun1,2, Shaoli Song1,2, Xiaoping Zhao1,2, Jianjun Liu1,2, Gang Huang1,2,3,4
1Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
2Institute of Clinical Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
3Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China
4Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
*These authors have contributed equally to this work
Gang Huang, email: [email protected]
Keywords: lung cancer, gefitinib, SREBP, chemotherapy, lipid metabolism
Received: October 12, 2015 Accepted: June 29, 2016 Published: July 20, 2016
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.
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