title: Ginsenoside Rh2 inhibits hepatocellular carcinoma through β-catenin and autophagy.
abstract: Hepatocellular carcinoma (HCC) is the most common liver cancer, with a very poor prognosis. There is an urgent need for an effective therapy for HCC. Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancer, whereas its effects on HCC have not been examined. Here, we treated human HCC cells with different doses of GRh2, and found that GRh2 dose-dependently reduced HCC viability, in either CCK-8 assay or MTT assay. The effects of GRh2 on the cancer stem cells (CSCs)-like cells were determined by aldefluor flow cytometry and by tumor sphere formation, showing that GRh2 dose-dependently decreased the number of these CSCs-like cells in HCC. Autophagy-associated protein and β-catenin level were measured in GRh2-treated HCC cells by Western blot, showing that GRh2 increased autophagy and inhibited β-catenin signaling. Expression of short hairpin small interfering RNA (shRNA) for Atg7 in HCC cells completely abolished the effects of GRh2 on β-catenin and cell viability, while overexpression of β-catenin abolished the effects of GRh2 on autophagy and cell viability. Together, our data suggest that GRh2 may inhibit HCC cell growth, possibly through a coordinated autophagy and β-catenin signaling.
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Leida
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; D051176:beta Catenin; C055305:ginsenoside Rh2