Cholesterol synthesis disruption combined with a molecule-targeted drug is a promising metabolic therapy for EGFR mutant non-small cell lung cancer.
Cholesterol synthesis disruption combined with a molecule-targeted drug is a promising metabolic therapy for EGFR mutant non-small cell lung cancer.
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DOI：
10.21037/tlcr-20-812
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发表时间：
2021-01
影响因子：
4
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Luo Y;Yang Y;Peng P;Zhan J;Wang Z;Zhu Z;Zhang Z;Liu L;Fang W;Zhang L
获得性耐药是表皮生长因子受体（EGFR）突变型非小细胞肺癌面临的挑战。在这里，我们提出了一种新的治疗策略的基础上，最近的脂质代谢工作。我们应用多种实验方法，如免疫印迹，MTT，si-RNA，和动物模型，以证明EGFR和低密度脂蛋白受体（LDLR）之间的关系，以及他汀类药物单药治疗，TKI单药治疗，以及它们的组合对细胞增殖的影响在细胞水平和动物水平。LDLR与EGFR呈正相关，EGFR信号通过SREBP-1依赖性通路上调LDLR表达，EGFR突变细胞依靠脂质生存和生长。阿托伐他汀与分子靶向药物联用，不仅在体外增强了治疗效果，而且在体内也减缓了NSCLC的生长。在本动物实验中，联合用药（阿托伐他汀与TKI）对NSCLC有较好的抑瘤效果。在HCC 827细胞系中，吉非替尼组的平均肿瘤缩小率约为68%，阿托伐他汀组约为49%，但联合组约为89%。在H1975细胞系中，奥希替尼组平均肿瘤缩小约为18%，阿托伐他汀组约为8%，但联合组约为44%。EGFR-TKI和他汀类药物的组合用于EGFR突变型NSCLC可能是一种新的肿瘤抑制治疗。
Acquired resistance is a challenge for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer. Here, we propose a novel treatment strategy based on recent lipid metabolism work. We applied a variety of experimental methods such as immunoblotting, MTT, si-RNA, and animal models, to demonstrate the relationship between EGFR and low-density lipoprotein receptor (LDLR) and the effects of statin monotherapy, and TKI monotherapy, and their combination on cell proliferation at the cell level and animal level. LDLR has a positive correlation with EGFR, EGFR signaling upregulates LDLR expression through the SREBP-1 dependent pathway, EGFR mutation cells count on lipids to survive and grow. Combined with a molecule-targeted drug, atorvastatin not only enhances the treatment effect in vitro, but also mitigates the growth of NSCLC in vivo. In this animal experiment, the combination medicine (atorvastatin with TKI) has a better tumor suppression effect on NSCLC. In HCC827 cell line, the average tumor shrinkage is about 68% in Gefitinib group, and about 49% in atorvastatin group, but about 89% in combination group. In H1975 cell line, the average tumor shrinkage is about 18% in Osimertinib group, and about 8% in atorvastatin group, but about 44% in combination group. the combination of an EGFR-TKI and a statin for EGFR mutant NSCLC may be a novel tumor inhibiting treatment.
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影响因子：
3
作者：
Chang TC;Chin YT;Nana AW;Wang SH;Liao YM;Chen YR;Shih YJ;Changou CA;Yang YS;Wang K;Whang-Peng J;Wang LS;Stain SC;Shih A;Lin HY;Wu CH;Davis PJ
通讯作者：
Davis PJ
CYP27A1通过调节胆固醇稳态抑制膀胱癌细胞增殖
影响因子：
4.3
作者：
Liang, Zhijuan;Chen, Yuanbin;Niu, Haitao
通讯作者：
Niu, Haitao
影响因子：
158.5
作者：
Soria, J. -C.;Ohe, Y.;Nguyen, Nhung
通讯作者：
Nguyen, Nhung
DOI：
10.1016/j.bbrc.2017.05.147
发表时间：
2017-07-29
影响因子：
3.1
作者：
Peng, Peng;Wei, Wei;Li, Jingwen
通讯作者：
Li, Jingwen
影响因子：
11.2
作者：
Kuzu OF;Noory MA;Robertson GP
通讯作者：
Robertson GP