Senegenin suppresses hepatocellular carcinoma by regulating O-GlcNAcylation  

作　　者：Xiang Zhang Li-Qiong Wang Zhi-Yong Liu 

机构地区：[1]Department of Traditional Chinese Medicine,Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University,Shanghai 201700,China [2]Department of Hepatology,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第9期3994-4005,共12页世界胃肠肿瘤学杂志（英文版）（电子版）

摘　　要：BACKGROUND Based on current knowledge,hepatocellular carcinoma(HCC)is a condition with numerous etiologies and risk factors.However,the pathogenesis of HCC remains unclear.AIM To investigate the roles of senegenin and O-GlcNAcylation in the growth and metastasis of HCC.METHODS The levels of O-linked N-acetylglucosamine transferase(OGT)and O-GlcNAcylation in HCC cells and tissues were detected using western blot analysis.The effects of senegenin and O-GlcNAcylation on the proliferation of HCC cells were investigated in vitro using cell counting kit-8 and clonogenic assays.The potential effects of senegenin and O-GlcNAcylation on HCC metastasis were examined using the transwell migration assay.O-GlcNAcylation levels were altered via drug treatment and lentiviral infection,and western blot analysis was used to detect proteins involved in various pathways.RESULTS Western blot analysis revealed that OGT and O-GlcNAcylation levels were significantly elevated in HCC tissues and cells.O-GlcNAcylation levels in HCC cells were significantly altered by drug treatment and lentiviral infection.An increase in the glycosylation level was linked to enhanced proliferation,invasiveness,clonogenicity,and metastatic potential of cancer cells.O-GlcNAcylation induced by senegenin was found to slow the proliferation and migration of HCC cells.The levels of proteins involved in nuclear factor-kappa B(NF-κB)and c-Jun N-terminal kinase(JNK)pathways,which are associated with endoplasmic reticulum stress,were altered.CONCLUSION Senegenin lowers O-GlcNAcylation levels,decreases OGT expression,and inhibits cancer cell growth and metastasis by regulating proteins involved in NF-κB and JNK pathways.

关 键 词：SENEGENIN O-GLCNACYLATION Liver cancer PATHOGENESIS METASTASIS 

分 类 号：R735.7[医药卫生—肿瘤] R459.3[医药卫生—临床医学]