Curcumin inhibits lipid metabolism in non-small cell lung cancer by downregulating the HIF-1α pathway.
10.12122/j.issn.1673-4254.2025.05.17
- Author:
Dandan LI
1
;
Jiaxin CHU
1
;
Yan YAN
2
;
Wenjun XU
3
;
Xingchun ZHU
3
;
Yun SUN
3
;
Haofeng DING
3
;
Li REN
4
;
Bo ZHU
1
Author Information
1. Department of Pathology, Bengbu Medical University, Bengbu 233000, China.
2. College of Laboratory Medicine, Bengbu Medical University, Bengbu 233000, China.
3. Department of Pathology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China.
4. Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China.
- Publication Type:Journal Article
- Keywords:
HIF-1α pathway;
curcumin;
lipid metabolism;
non-small cell lung cancer
- MeSH:
Curcumin/pharmacology*;
Humans;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*;
Animals;
Lipid Metabolism/drug effects*;
Carcinoma, Non-Small-Cell Lung/pathology*;
Lung Neoplasms/pathology*;
Mice, Nude;
Down-Regulation;
Mice;
Cell Proliferation/drug effects*;
Cell Line, Tumor;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha;
PPAR alpha/metabolism*;
Signal Transduction/drug effects*;
A549 Cells
- From:
Journal of Southern Medical University
2025;45(5):1039-1046
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism.
METHODS:The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets.
RESULTS:Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells.
CONCLUSIONS:Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
