中国药理学与毒理学杂志2025，Vol.39Issue(11)：839-846,8.DOI:10.3867/j.issn.1000-3002.2025.08255
雷公藤红素抑制三阴性乳腺癌细胞脂滴积累和调节脂质代谢的研究
Celastrol inhibits lipid droplet accumulation and modulates lipid metabolism in triple-negative breast cancer cells
摘要
Abstract
OBJECTIVE To investigate the effect of celastrol(Cel)on lipid droplet accumulation in triple-negative breast cancer cells promoted by adipocytes in the tumor microenvironment.METHODS 3T3-L1 preadipocytes were differentiated into mature adipocytes using an adipogenic induction kit,with lipid droplet distribution assessed by Oil Red O staining.Adipocytes-derived conditioned medium(Adi-CM)was collected 2 days post-differentiation.4T1 cells were divided into control and Adi-CM groups(25%,50%and 75%)and cultured for 48 h.Cell viability was measured by CCK-8 assay,and lipid droplet accumulation was quantified via Oil Red O staining to determine the optimal Adi-CM concentration.For Cel treatment,4T1 cells exposed to 75%Adi-CM were assigned to control and Cel groups(0.2,0.4,0.8,1.6,3.2 and 6.4 μmol·L-1),with viability assessed after 48 h to establish Cel dosing.Subsequent experiments involved control,Adi-CM(75%),and Adi-CM-Cel(0.8 μmol·L-1)groups.Lipid droplets were extracted using a lipid droplet isolation kit,and lipid composition was analyzed by high-resolution liquid chromatography-mass spectrometry.RESULTS Twenty days into differentiation,3T3-L1 preadi-pocytes exhibited abundant intracellular lipid droplets as confirmed by Oil Red O staining,and Adi-CM was collected 2 days post-maturation.Compared to the control group,4T1 cells treated with 75%Adi-CM demonstrated a significant increase in viability and maximal lipid droplet accumulation.Cel at concen-trations below 0.8 μmol·L-1 maintained 4T1 cell viability above 70%while dose-dependently suppressing lipid droplet accumulation.Lipidomic profiling revealed 22 differentially expressed lipid species between the 75%Adi-CM group and control group,which were predominantly upregulated.Cel treatment did not alter lipid species diversity but reduced their abundance,with notable inhibition of phosphatidylethanol-amine expression levels.CONCLUSION Cel inhibits tumor cell proliferation by suppressing Adi-CM-induced lipid droplet accumulation and modulating lipid contents in 4T1 cells.关键词
雷公藤红素/脂肪细胞/乳腺癌细胞/脂滴/脂质/高分辨液质联用法Key words
celastrol/adipocytes/breast cancer cells/lipid droplets/lipids/high-resolution liquid chromatography-mass spectrometry分类
医药卫生引用本文复制引用
马宁辉,许紫怡,叶宇豪,熊阳..雷公藤红素抑制三阴性乳腺癌细胞脂滴积累和调节脂质代谢的研究[J].中国药理学与毒理学杂志,2025,39(11):839-846,8.基金项目
国家自然科学基金(82174095) （82174095）
浙江省医药卫生科技项目(2021KY813) National Natural Science Foundation of China(82174095) （2021KY813）
and Medical Health Science and Technology Project of Zhejiang Provincial(2021KY813) （2021KY813）
