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作 者:Qian Wu Yong-bin Wang Xiao-wen Che Hui Wang Wei Wang
出 处:《Journal of Integrative Medicine》2023年第3期268-276,共9页结合医学学报(英文版)
基 金:supported by the National Natural Science Foundation of China(Grant No.81973630);National Clinical Key Specialty Project Foundation(Grant No.Z155080000004).
摘 要:Objective:Although there have been improvements in targeted therapy and immunotherapy,the majority of lung adenocarcinoma(LUAD)patients still lack effective therapies.Consequently,it is urgent to screen for new diagnosis biomarkers and pharmacological targets.Junctional adhesion molecule-like protein(JAML)was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD.Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD.However,the effect of kaempferol on JAML is still unknown.Methods:Small interfering RNA was used to knockdown JAML expression.The cell viability was determined using the cell counting kit-8 assay.The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay.The migration and invasion of LUAD cells were evaluated by transwell assays.Molecular mechanisms were explored by Western blotting.Results:JAML knockdown suppressed proliferation,migration and invasion of LUAD cells,and JAML deficiency restrained epithelial-mesenchymal transition(EMT)via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.Using a PI3K activator(740Y-P),rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway.Kaempferol also inhibited proliferation,migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway.Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells.Kaempferol exerted anticancer effects by targeting JAML.Conclusion:JAML is a novel target for kaempferol against LUAD cells.
关 键 词:Junctional adhesion molecule-like protein KAEMPFEROL Lung adenocarcinoma PROLIFERATION INVASION MIGRATION
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