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Apolipoprotein B100 acts as a tumor suppressor in ovarian cancer via lipid/ER stress axis-induced blockade of autophagy

摘要Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy.As autophagy is a vital cellular process for maintaining homeostasis,targeting the autophagic pathway has emerged as an avenue for cancer therapy.In the present study,we identify apolipoprotein B100(ApoB100),a key modulator of lipid metabolism,as a potential prognostic biomarker of ovarian cancer.ApoB100 functioned as a tumor suppressor in ovarian cancer,and the knockdown of ApoB100 promoted ovarian cancer progression in vivo.Moreover,ApoB100 blocked autophagic flux,which was dependent on interfering with the lipid accumulation/endoplasmic reticulum(ER)stress axis.The effects of LFG-500,a novel synthetic flavonoid,on ApoB100 induction were confirmed using proteomics and lipidomics analyses.Herein,LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100.Moreover,data from in vivo experiments further demonstrated that ApoB100,as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy,were responsible for the anti-tumor effects of LFG-500 on ovarian cancer.Hence,our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment.

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作者 Ze-yuan Yin [1] Shi-min He [2] Xin-yuan Zhang [3] Xiao-chen Yu [3] Kai-xuan Sheng [3] Tong Fu [4] Yi-xue Jiang [5] Liu Xu [3] Bing-xuan Hu [6] Jing-bo Zhang [4] Yan-yu Li [4] Qing Wang [4] Bei-bei Zhang [3] Yun-meng Qi [4] Joseph Adu-Amankwaah [7] Xue-yan Zhou [3] Qi Qi [8] Bei Zhang [9] Cheng-lin Li [3] 学术成果认领
作者单位 The First Clinical Medical School,Xuzhou Medical University,Xuzhou 221004,China;Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;Department of Cardiology,Affiliated Hospital of Xuzhou Medical University,Xuzhou 221004,China;Cardiovascular Sciences,The University of Manchester,Manchester M13 9NT,UK [1] Department of Obstetrics and Gynecology,Xuzhou Central Hospital,Xuzhou Clinical School of Xuzhou Medical University,Xuzhou 221009,China;Department of Obstetrics and Gynecology,Zhenjiang Fourth People's Hospital,Zhenjiang 212001,China [2] Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004,China [3] Department of Obstetrics and Gynecology,Xuzhou Central Hospital,Xuzhou Clinical School of Xuzhou Medical University,Xuzhou 221009,China [4] Xuzhou Center for Disease Control and Prevention,Xuzhou 221002,China [5] The First Clinical Medical School,Xuzhou Medical University,Xuzhou 221004,China [6] Department of Physiology,Xuzhou Medical University,Xuzhou 221004,China [7] State Key Laboratory of Bioactive Molecules and Drug Ability Assessment;MOE Key Laboratory of Tumor Molecular Biology;Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research;Department of Pharmacology,School of Medicine,Jinan University,Guangzhou 510632,China [8] Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;Department of Obstetrics and Gynecology,Xuzhou Central Hospital,Xuzhou Clinical School of Xuzhou Medical University,Xuzhou 221009,China [9]
DOI 10.1038/s41401-024-01470-x
发布时间 2025-05-29(万方平台首次上网日期,不代表论文的发表时间)
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中国药理学报(英文版)

中国药理学报(英文版)

2025年46卷5期

1445-1461页

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