期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 36, 期 2, 页码 499-508出版社
KARGER
DOI: 10.1159/000430115
关键词
Skin squamous cell carcinoma (SCC); Cancer stem cells (CSCs); Lgr5; Ginsenoside Rh2 (GRh2); beta-catenin
资金
- National Natural Science Foundation Project [81401250, 81372051]
- Medical and Senile Disease Foundation Project of General Staff Headquarters [ZCWS14B06]
- 309 Hospital of PLA Foundation Project [2014MS-001]
- National Key Basic Research Development Program (973 Program) [2012CB518104]
- Military Medical Key foundation [BWS11C061]
Background/Aims: 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 flow cytometry and by tumor sphere formation. Autophagy-associated protein and beta-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and beta-catenin were used to inhibit autophagy and beta-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 beta-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on beta-catenin and cell viability, while increasing beta-catenin abolished the effects of GRh2 on autophagy and cell viability. Conclusion: 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 beta-catenin signaling. Copyright (C) 2015 S. Karger AG, Basel
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