Curcumol Retards Progression of Non-Small Cell Lung Cancer through the SREBP-1/FASN/EGFR Pathway

OBJECTIVE To investigate the effect of Curcumol on lipid metabolism in non-small cell lung cancer (NSCLC) and its related molecular mechanism.

METHODS A nude mouse xenograft tumor model was established, and Curcumol was administered for 14 d. The volume and weight of subcutaneous tumors were recorded. Hematoxylin-eosin (HE) and immunohistochemical staining were used to observe the pathological morphology of tumor tissues and organs, as well as the expression levels of Ki67 protein. Biochemical kits were used to detect the levels of lipids in tumor tissues. Western blot was used to detect the expression levels of SREBP-1, FASN, and EGFR proteins in tumor tissues. The qPCR and immunofluorescence were used to detect the expression of SREBP-1 in tumor tissues. Curcumol was used to treat human NSCLC cell line A549 and A549 cells overexpressing SREBP-1. The EdU assay was used to detect the proliferation ability of lung cancer cells; the MTT colorimetric method was used to detect cell viability; the Transwell assay was used to detect tumor cell migration and invasion; flow cytometry was used to detect cell apoptosis; biochemical kits were used to detect lipid levels in cells; and Western blot was used to detect the expression levels of SREBP-1, FASN, and EGFR proteins.

RESULTS In the in vivo experiment, compared with the control group, Curcumol significantly inhibited the growth of subcutaneous xenografts, inhibited tumor cell proliferation(P < 0.05, P < 0.01), reduced the levels of triglycerides (TG), total cholesterol (T-CHO), and free fatty acids (FFA) in tumor tissues(P < 0.05, P < 0.01), downregulated the expression of SREBP-1, FASN, and p-EGFR proteins(P < 0.01), and inhibited the expression of SREBP-1 mRNA in tumor tissues(P < 0.05, P < 0.01). In the in vitro experiment, compared with the control group, Curcumol significantly inhibited the proliferation, migration, and invasion of A549 cells, reduced cell viability(P < 0.05, P < 0.01), promoted tumor cell apoptosis(P < 0.01), downregulated the levels of FFA, T-CHO, and TG in A549 cells(P < 0.05, P < 0.01), and inhibited the expression of SREBP-1, FASN, and p-EGFR proteins(P < 0.05, P < 0.01). Additionally, overexpression of SREBP-1 antagonized the inhibitory effects of Curcumol on lipid synthesis and EGFR activation, and weakened the inhibitory effects of Curcumolc on tumor cells.

CONCLUSION Curcumol inhibits the expression levels of SREBP-1 and FASN, reduces lipid synthesis, blocks EGFR signal transduction, and slows down the occurrence and development of NSCLC.