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

This study aimed to develop lung CSCs that stably express stem cell properties through transfection t o 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 lea ves 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 apopto sis, 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 sangu inarine may be a natural antitumor compound that targets lung CSCs, laying a foundation for further clinical study.
Source: Tumor Biology - Category: Cancer & Oncology Source Type: research