NDLI: Construction and application of a lung cancer stem cell model: antitumor drug screening and molecular mechanism of the inhibitory effects of sanguinarine

Content Provider	Springer Nature Link
Author	Yang, Jia Fang, Zhihong Wu, Jianchun Yin, Xiaoling Fang, Yuan Zhao, Fanchen Zhu, Shiguo Li, Yan
Copyright Year	2016
Abstract	Lung cancer is a neoplasm with a 5-year survival rate of less than 15 % and a leading cause of death worldwide, despite recent progress in treatment and diagnostic methods. Lung cancer stem-like cells (CSCs) are pivotal in lung cancer metastasis and drug resistance. This study aimed to develop lung CSCs that stably express stem cell properties through transfection to further screen traditional Chinese herbal compounds. Lung adenocarcinoma stem cells, which include various phenotypic subgroups, are normally characterized by high expression levels of pluripotent stem cell genes, particularly Nanog and OCT4. Plasmids containing Nanog and OCT4 were constructed and transfected into cells, and lung CSCs were identified not only in vitro using RT-PCR, Western blotting, plate cloning, sphere formation, drug resistance, and transwell migration but also in vivo using a nude mouse tumorigenicity assay. Subsequently, sanguinarine, which is derived from the whole leaves of the traditional Chinese medicine celandine, was identified through the high-throughput screening of a small-molecule compound library. Investigation of the molecular mechanisms of the effects of sanguinarine revealed that it significantly inhibited lung CSC proliferation, invasion, and apoptosis, possibly via downregulation of the Wnt/β-catenin signaling pathway. Our results indicate that lung CSCs established by gene transfection may provide a stable and effective method of constructing CSCs to effectively screen potential antitumor drugs. Furthermore, these results suggest that sanguinarine may be a natural antitumor compound that targets lung CSCs, laying a foundation for further clinical study.
Starting Page	13871
Ending Page	13883
Page Count	13
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	10
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-08-02
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Lung cancer stem cell Antitumor drug screen Molecular mechanism Sanguinarine Wnt/β-catenin signaling Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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