【摘 要】
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Hepatocellular carcinoma(HCC),the most prevalent liver cancer,is considered one of the most lethal malignancies with a dismal outcome mainly due to frequent intrahepatic and distant metastasis.In the present study,we demonstrated that oroxylin A,a natural
【机 构】
：
State Key Laboratory of Natural Medicines,School of Basic Medicine and Clinical Pharmacy,China Pharm
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Hepatocellular carcinoma(HCC),the most prevalent liver cancer,is considered one of the most lethal malignancies with a dismal outcome mainly due to frequent intrahepatic and distant metastasis.In the present study,we demonstrated that oroxylin A,a natural product extracted from Scutellaria radix,significantly inhibits transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)and metastasis in HCC.Oroxylin A blocked the TGF-β1/Smad signaling via upregulating the non-steroidal anti-inflammatory drug-activated gene-1(NAG-1)expression.Oroxylin A promoted NAG-1 transcription by regulating the acetylation of CCAAT/enhancer binding protein β(C/EBPβ),a transcription factor that binds to the NAG-1 promoter.In terms of the underlying mechanism,oroxylin A may interact with histone deacetylase 1(HDAC1)by forming hydrogen bonds with GLY149 residue and induce proteasome-mediated degradation of HDAC1 subsequently impairing HDAC1-mediated deacetylation of C/EBPβ and promoting the expression of NAG-1.Taken together,our findings revealed a previously unknown tumor-suppressive mechanism of oroxylin A.Oroxylin A should be further investigated as a potential clinical candidate for inhibiting HCC metastasis.
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