南方医科大学学报2025,Vol.45Issue(5):1039-1046,8.DOI:10.12122/j.issn.1673-4254.2025.05.17
姜黄素通过下调HIF-1α通路抑制非小细胞肺癌脂质代谢
Curcumin inhibits lipid metabolism in non-small cell lung cancer by downregulating the HIF-1α pathway
摘要
Abstract
Objective 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.Conclusion Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.关键词
姜黄素/非小细胞肺癌/脂质代谢/HIF-1α通路Key words
curcumin/non-small cell lung cancer/lipid metabolism/HIF-1α pathway引用本文复制引用
李丹丹,楚佳鑫,闫妍,徐文隽,朱行春,孙韵,丁浩峰,任丽,朱博..姜黄素通过下调HIF-1α通路抑制非小细胞肺癌脂质代谢[J].南方医科大学学报,2025,45(5):1039-1046,8.基金项目
安徽省高校自然科学研究项目(2023AH051998) (2023AH051998)
安徽省高等学校科学研究项目(2022AH051526) (2022AH051526)
蚌埠医科大学研究生科研创新计划项目(Byycx23066) (Byycx23066)