Daidzein Suppresses Tumor Necrosis Factor-α Induced Migration and Invasion by Inhibiting Hedgehog/Glil Signaling in Human Breast Cancer Cells

摘要

In breast cancer, the cytokine tumor necrosis factor-a (TNF-a) induces cell invasion, although the molecular basis of it has not been clearly elucidated In this study, we investigated the role of daidzein in regulating TNF-a induced cell invasion and the underlying molecular mechanisms Daidzein inhibited TNF-a induced cellular migration and invasion in estrogen receptor (ER) negative MCFlODCISxom human breast cancer cells. TNF-α activated Hedgehog (Hh) signaling by enhancing Glil nuclear translocation and transcriptional activity, which resulted in increased invasiveness} these effects were blocked by daidzein and the Hh signaling inhibitors, cyclopamine and visraodegib. Moreover, these compounds suppressed TNF-a induced matrix rnetalloproteinase (MMP)-9 mRNA expression and activity. Taken together, mammary tumor cell invasiveness was stimulated by TNF-a induced activation of Hh signaling; these effects weie abrogated by daidzein, which suppressed Glii activation, thereby inhibiting migration and invasion