title: Differentiation therapy of hepatocellular carcinoma by inhibiting the activity of AKT/GSK-3β/β-catenin axis and TGF-β induced EMT with sophocarpine.
abstract: Hepatocellular carcinoma progression is thought to be driven by cancer stem cells (CSCs). No clinical trial has, as yet, shown convincing long-term disease free survival results for the majority of patients in HCC. So it is important to discover new anti-cancer agents. In our study, we chose sophocarpine, which is derived from the foxtail-like sophora herb, for its efficacy to inhibit HCC including CSCs and potential mechanism study. Our results show that sophocarpine could not only reduce HCC cell viability, eliminate HCC and reverse hepatoma cells malignant phenotype, but also reduce the ratio of CSCs and inhibit the sphere formation of CSCs in vitro. In vivo, sophocarpine significantly displayed antitumor effects in subcutaneous xenograft HCC models and orthotopic transplantation tumor models. Further studies showed that sophocarpine could exert anti-tumor effects partly via downregulating the activity of the cancer stem cell related pathways and inhibiting EMT induced by TGF-β.
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Pei-Qin
authors.initials: PQ
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Qiao
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Second Military Medical University, Shanghai 200043, China.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Wei-Fen
authors.initials: WF
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Zong-Li
authors.initials: ZL
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhao-Shen
authors.initials: ZS
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: chenyuexiang@hotmail.com.
authors.forename: Yue-Xiang
authors.initials: YX
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051177:Catenins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D051177:Catenins; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D016212:Transforming Growth Factor beta; C035933:sophocarpine; D000093842:Matrines; C000605506:GSK3B protein, human
keywords: CSC; Differentiation; EpCAM; Hepatocellular carcinoma; Sophocarpine