Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells.
Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells.
复制标题
抑制 SREBP 会增加非小细胞肺癌细胞对吉非替尼的敏感性。
DOI：
10.18632/oncotarget.10721
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发表时间：
2016-08-09
期刊：
影响因子：
--
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Li J;Yan H;Zhao L;Jia W;Yang H;Liu L;Zhou X;Miao P;Sun X;Song S;Zhao X;Liu J;Huang G
EGFR抑制剂在肺癌患者中的临床成功受到不可避免的治疗耐药性发展的限制。在这里，我们表明，抑制SREBP增加吉非替尼在体外和体内的敏感性。SREBP 1结合伴侣MARVELD 1的干扰也增强了吉非替尼的治疗效果。在机制上，SREBP抑制降低细胞膜流动性，导致EGFR酪氨酸磷酸化降低。因此，靶向脂质代谢联合EGFR-TKI可能是一种新的肿瘤治疗策略。
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.