Identification of solamargine as a cisplatin sensitizer through phenotypical screening in cisplatin-resistant NSCLC organoids.
cisplatin resistance
hedgehog
lung cancer
patient-derived organoids
solamargine
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
26
10
2021
accepted:
14
07
2022
entrez:
29
8
2022
pubmed:
30
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
Although Cisplatin (DDP) is a widely used first-line chemotherapy medication, DDP resistance is one of the main causes of treatment failure in advanced lung cancer. Therefore, it is urgent to identify DDP sensitizers and investigate the underlying molecular mechanisms. Here we utilized DDP-resistant organoids established from tumor biopsies of patients with relapsed lung cancers. In this study, we identified Solamargine as a potential DDP sensitizer through screening a natural product library. Mechanically, Solamargine induced G0/G1-phase arrest and apoptosis in DDP-resistant lung cancer cell lines. Gene expression analysis and KEGG pathway analysis indicated that the hedgehog pathway was suppressed by Solamargine. Moreover, Gli responsive element (GRE) reporter gene assay and BODIPY-cyclopamine binding assay showed that Solamargine inhibited the hedgehog pathway via direct binding to SMO protein. Interestingly, Solamargine and DDP showed a synergetic effect in inhibiting DDP-resistant lung cancer cell lines. Taken together, our work herein revealed Solamargine as a hedgehog pathway inhibitor and DDP-sensitizer, which might provide a new direction for further treatment of advanced DDP-resistant lung cancer patients.
Identifiants
pubmed: 36034794
doi: 10.3389/fphar.2022.802168
pii: 802168
pmc: PMC9399411
doi:
Types de publication
Journal Article
Langues
eng
Pagination
802168Informations de copyright
Copyright © 2022 Han, Shi, Xu, Zhang, Cao, Yu, Li and Xu.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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