摘要
Tumor angiogenesis is closely related to tumor development,immune escape,and drug resistance.Therefore,the development of effective anti-tumor angiogenesis drugs is of great research significance.Although the current clinical angiogenesis inhibitors have achieved certain efficacy,they also pose the problems of limited and short duration of efficacy,drug resistance,and intrinsic toxicity.Anti-tumor angiogenesis strategies targeting endothelial cells(ECs)have attracted widespread attention in the development of highly effective and low toxicity anti-angiogenesis inhibitors.Studies have verified that the trace element selenium(Se)can inhibit tumor growth by inhibiting tumor angiogenesis through different mechanisms.Nevertheless,it is unclear whether Se speciation has different effects on anti-tumor angiogenesis.Herein,we found that Se exhibited effective anti-angiogenic activity,and its mechanisms of activity were determined by its chemical speciation.Organic Se can significantly inhibit tumor angiogenesis by targeting thioredoxin reductase(TrxR)to trigger cell apoptosis and cell cycle arrest and by increasing reactive oxygen species(ROS)production in ECs.Inorganic Se can induce cell cycle arrest and increase ROS production in ECs,showing promising anti-angiogenic effects.Se nanoparticles(SeNPs)slightly inhibit tumor angiogenesis by inducing apoptosis and cell cycle arrest and by increasing the production of ROS.In summary,this study elucidates the anti-angiogenic activity of Se speciation control with a view to providing a scientific reference for the design and development of novel Se-based highly effective and low toxicity angiogenesis inhibitors.
基金
funded by Science and Technology Projects in Guangzhou(No.202102010083)
National Natural Science Foundation of China(No.32201062)
Guangzhou Basic and Applied Basic Research Foundation(No.202201010339).
