Oroxylin A inhibits the migration of hepatocellular carcinoma cells by inducing NAG-1 expression  

作　　者：Tong-xin Huo Xiao-ping Wang Zhou Yu Bo Kong Yuan He Qing-long Guo Xiao-bo Zhang Lei Qiang 

机构地区：[1]State Key Laboratory of Natural Medicines,School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198,China [2]State Key Laboratory of Natural Medicines,Jiangsu Key Laboratory of Carcinogenesis and Intervention,School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210009,China [3]Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs,Institute of Dermatology,Chinese Academy of Medical Sciences&Peking Union Medical College,Nanjing 210042,China

出　　处：《Acta Pharmacologica Sinica》2022年第3期724-734,共11页中国药理学报（英文版）

基　　金：This work was supported by the General Program of National Natural Science Foundation of China(81772911,81973522,81974425,and 81903648);the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX20-0654);the Natural Science Foundation of Jiangsu Province(BK20170744);the Six Talent Peaks Project in Jiangsu Province(SWYY-095).

摘　　要：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 proteinβ(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/EBPβand 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.

关 键 词：hepatocellular carcinoma METASTASIS oroxylin A NAG-1 HDAC1 

分 类 号：R965[医药卫生—药理学]