Transl Lung Cancer Res. 2021 Jan;10(1):
128-142
Background: 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.Methods: 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.
Results: 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.
Conclusions: the combination of an EGFR-TKI and a statin for EGFR mutant NSCLC may be a novel tumor inhibiting treatment.
Keywords: Non-small cell lung cancer (NSCLC); cholesterol; epidermal growth factor receptor (EGFR); low-density lipoprotein receptor (LDLR); metabolic therapy