EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT
Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment.EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound.In this study,we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells.We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase.We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm,MD stimulation by GROMACS,5PR assay and elastase enzymatic activity assay.As the natural inhibitor of neutrophil elastase,α1-antitrypsin is synthesized in tumor cells.We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastasetreated A549 cells.We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the Pl3K/Akt pathway.Overall,our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells.The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.
Yilixiati Xiaokaiti Haoming Wu Ya Chen Haopeng Yang Jianhui Duan Xin Li Yan Pan Lu Tie Liangren Zhang Xuejun Li
State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China;Departme Department of Immunology,Peking University Health Science Center,Beijing 100191,China State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China;School o
国内会议
大连
英文
355-368
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）