Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells  

作　　者：WEIXUE WANG TONGTONG WANG YAN ZHANG TING DENG HAIYANG ZHANG YI BA 

机构地区：[1]Department of GI Medical Oncology,Tanjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin's Clinical Research Center for Cancer,Tianjin Key Iaboratory of Digestive Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin,300060,China

出　　处：《Oncology Research》2024年第3期489-502,共14页肿瘤学研究（英文）

基　　金：grants from the National Science Foundation of China(Nos.82173125,81974374,82072664,82103677);Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-009A);The Science&Technology Development Fund of Tianjin Education Commission for Higher Education(2020KJ127).

摘　　要：Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell death.Apatinib is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis pathway.However,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported yet.Tumor.secreted exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered.Here,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of Apatinib.In conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

关 键 词：Cellular ferroptosis EXOSOME Tyrosine kinase inhibitor Gastrointestinal tumors miRNA 

分 类 号：R730[医药卫生—肿瘤]