中国药理学通报2025，Vol.41Issue(5)：898-907,10.DOI:10.12360/CPB202406019
p-AMPK介导的不同亚型乳腺癌细胞自噬及其分子机制
Autophagy in different subtypes of breast cancer cells mediated by p-AMPK and its molecular mechanisms
摘要
Abstract
Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.关键词
p-AMPK/乳腺癌/饥饿诱导/雌激素受体/自噬/MTORKey words
p-AMPK/breast cancer/starvation induc-tion/estrogen receptor/autophagy/MTOR分类
医药卫生引用本文复制引用
杨鑫娇,胡汝瑶,熊喆,邹迪,蔡洁,夏从龙,白忠彬,赵红业..p-AMPK介导的不同亚型乳腺癌细胞自噬及其分子机制[J].中国药理学通报,2025,41(5):898-907,10.基金项目
国家自然科学基金资助项目(No 81872452) （No 81872452）
