title: Ginsenoside rh2 inhibits cancer stem-like cells in skin squamous cell carcinoma.
abstract: OBJECTIVE
  Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined.
  
  
  METHODS
  Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and β-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and β-catenin were used to inhibit autophagy and β-catenin signaling pathway, respectively, as loss-of-function experiments.
  
  
  RESULTS
  We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced β-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on β-catenin and cell viability, while increasing β-catenin abolished the effects of GRh2 on autophagy and cell viability.
  
  
  CONCLUSIONS
  Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and β-catenin signaling.
authors.affiliation: Department of Burns and Plastic Surgery, General Hospital of Jinan Military Region, Jinan, China.
authors.forename: Shunli
authors.initials: S
authors.lastname: Liu
authors.forename: Mingrui
authors.initials: M
authors.lastname: Chen
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Li
authors.forename: Yujia
authors.initials: Y
authors.lastname: Wu
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Chang
authors.forename: Yabin
authors.initials: Y
authors.lastname: Qiu
authors.forename: Ling
authors.initials: L
authors.lastname: Cao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Chiyu
authors.initials: C
authors.lastname: Jia
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D051176:beta Catenin; C055305:ginsenoside Rh2