DOI: 10.1002/ame2.12527
Exploring the co-morbid relationship between Alzheimer's disease and lung cancer in the 5xFAD transgenic mouse model
Mingfeng Li1
Xinghan Wu1
Lin Jiang1
Min Liu1
Gong Yanju1
Xiaomeng Li1
Fan Tian1
Fan Ye1
Jinlong Wang1
Siyuan Wang1
Chuan Qin2
Ling Zhang1
1.NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,International Center for Technology and Innovation of Animal Model,Comparative Medicine Center,Institute of Laboratory Animal Sciences,Peking Union Medical College(PUMC),Chinese Academy of Medical Sciences(CAMS),Beijing,China2.NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,International Center for Technology and Innovation of Animal Model,Comparative Medicine Center,Institute of Laboratory Animal Sciences,Peking Union Medical College(PUMC),Chinese Academy of Medical Sciences(CAMS),Beijing,China;Changping National Laboratory(CPNL),Beijing,China
摘要：Background:Alzheimer's disease(AD)and lung cancer are leading causes of mortality among the older population.Epidemiological evidence suggests an antagonistic rela-tionship between them,whereby patients with AD exhibit a reduced risk of develop-ing cancer and vice versa.However,the precise mechanism by which AD antagonizes lung cancer progression warrants further elucidation.
Methods:To this end,we established a co-morbidity model using 5xFAD transgenic mice induced with the carcinogen urethane.We visualized and quantified surface lung tumor colonies,assessed pathological parameters associated with lung cancer and AD using histopathological analysis,and employed single-cell sequencing and molecular pathological analyses to explore the mechanisms by which AD confers resistance to lung cancer.
Results:Our findings revealed a significant reduction in lung tumor incidence in the AD group compared with that in the wild-type(WT)group.The results indicated a close association between AD-induced inhibition of lung tumor progression and iron homeostasis imbalance and increased oxidative stress.Moreover,greater CD8+T cy-totoxic lymphocyte and effector natural killer cell infiltration in the lung tumor tissues of AD mice and enhanced CD8+T cytotoxic lymphocyte-mediated killing of target cells may be the primary factors contributing to the inhibition of lung tumor growth in the presence of AD.
Conclusion:This study identified essential mechanisms through which AD suppresses lung tumorigenesis,thereby providing targets for potential therapeutic interventions in these diseases.
机标关键词：transgenicrelationshipalzheimerbetweencancermousemodel5xfad
论文发表日期：2025-03-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 784-797 )
英文信息