title: Actinidia chinensis Planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3 expression.
abstract: A wide range of studies has demonstrated the potent anticancer activity of Chinese herbs. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis root extract (acRoots) on hepatocellular carcinoma (HCC). HepG2 HCC cells were treated with various concentrations of acRoots for 72 h and examined by mRNA expression profiling, revealing alterations in cellular immunity, inflammation, proliferation, cell cycle, and metabolic signaling responses. Further analysis of the altered genes in cellular immunity and inflammation gene clusters identified prostaglandin E receptor 3 (EP3) as a key regulator of gene expression in response to acRoots. Further analysis revealed inhibition of cell growth, migration, and invasion in HCC in response to acRoots, along with increased apoptosis due to downregulation of EP3 expression. Treatment with acRoots and EP3 antagonist L-798106 led to decreases in VEGF, EGFR, MMP2, and MMP9 expression in HCC cells, along with significant effects on growth, migration, invasion, and apoptosis; the effects were reversed/blocked by the EP3 agonist sulprostone. Taken together, these data clearly demonstrated that acRoots inhibit HCC cell invasion and metastasis via inhibition of EP3 expression, resulting in decreased activation of VEGF, EGFR, MMP2, and MMP9.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Shanghai, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Fang
authors.affiliation: Clinical Science Institute, Zhongshan Hospital, Shanghai, China.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Hou
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Shanghai, China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: He
authors.affiliation: Clinical Science Institute, Zhongshan Hospital, Shanghai, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Clinical Science Institute, Zhongshan Hospital, Shanghai, China.
authors.forename: Minghuan
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Clinical Science Institute, Zhongshan Hospital, Shanghai, China. xiangdong.wang@clintransmed.org.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Shanghai, China. xiajinglin@fudan.edu.cn.|Minhang Hospital, Shanghai Medical School of Fudan University, Shanghai, 201100, China. xiajinglin@fudan.edu.cn.
authors.forename: Jinglin
authors.initials: J
authors.lastname: Xia
mesh_terms: D029042:Actinidia / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D015232:Dinoprostone; D009363:Neoplasm Proteins; D010936:Plant Extracts; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013449:Sulfonamides; C000595268:5-bromo-2-methoxy-N-(3-(naphthalen-2-yl-methylphenyl)acryloyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C545647:PTGER3 protein, human; C016767:sulprostone
keywords: Actinidia chinensis; Hepatocellular carcinoma; Immunity; Prostaglandin E receptor 3