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

// Jiajin Li 1, 2, * , Hui Yan 1, 2, * , Li Zhao 1, 2 , Wenzhi Jia 1, 2 , Hao Yang 3 , Liu Liu 1, 2 , Xiang Zhou 1, 2 , Ping Miao 1, 2 , Xiaoguang Sun 1, 2 , Shaoli Song 1, 2 , Xiaoping Zhao 1, 2 , Jianjun Liu 1, 2 , Gang Huang 1, 2, 3, 4 1 Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China 2 Institute of Clinical Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China 3 Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China 4 Shanghai University of Medicine and Health Sciences, Shanghai 201318, China * These authors have contributed equally to this work Correspondence to: Gang Huang, email: huang2802@163.com Keywords: lung cancer, gefitinib, SREBP, chemotherapy, lipid metabolism Received: October 12, 2015      Accepted: June 29, 2016      Published: July 20, 2016 ABSTRACT 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.