Luo Youli, Yang Yunpeng, Peng Peijian, Zhan Jianhua, Wang Zhihui, Zhu Zhiquan, Zhang Zhonghan, Liu Lin, Fang Wenfeng, Zhang Li
Department of Medical Oncology, Center for Interventional Medicine, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Transl Lung Cancer Res. 2021 Jan;10(1):128-142. doi: 10.21037/tlcr-20-812.
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 , but also mitigates the growth of NSCLC . 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.
获得性耐药是表皮生长因子受体（EGFR）突变的非小细胞肺癌面临的一项挑战。在此，我们基于近期的脂质代谢研究提出一种新的治疗策略。
我们应用了多种实验方法，如免疫印迹、MTT、小干扰RNA和动物模型，以证明EGFR与低密度脂蛋白受体（LDLR）之间的关系，以及他汀类药物单药治疗、酪氨酸激酶抑制剂（TKI）单药治疗及其联合治疗在细胞水平和动物水平对细胞增殖的影响。
LDLR与EGFR呈正相关，EGFR信号通路通过固醇调节元件结合蛋白-1（SREBP-1）依赖的途径上调LDLR表达，EGFR突变细胞依靠脂质存活和生长。与分子靶向药物联合使用时，阿托伐他汀不仅增强了治疗效果，还抑制了非小细胞肺癌的生长。在该动物实验中，联合用药（阿托伐他汀与TKI）对非小细胞肺癌具有更好的肿瘤抑制作用。在HCC827细胞系中，吉非替尼组的平均肿瘤缩小约为68%，阿托伐他汀组约为49%，而联合组约为89%。在H1975细胞系中，奥希替尼组的平均肿瘤缩小约为18%，阿托伐他汀组约为8%，而联合组约为44%。
EGFR-TKI与他汀类药物联合用于EGFR突变的非小细胞肺癌可能是一种新型的肿瘤抑制治疗方法。
