Magnoflorine inhibits the malignant phenotypes and increases cisplatin sensitivity of osteosarcoma cells via regulating miR-410-3p/HMGB1/NF-κB pathway.
Aporphines
/ pharmacology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cisplatin
/ pharmacology
Down-Regulation
/ drug effects
Epithelial-Mesenchymal Transition
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
HMGB1 Protein
/ metabolism
Humans
MicroRNAs
/ genetics
NF-kappa B
/ metabolism
Neoplasm Invasiveness
Osteosarcoma
/ genetics
Phenotype
Signal Transduction
/ drug effects
Up-Regulation
/ drug effects
Cisplatin sensitivity
Magnoflorine
Malignant phenotypes
Osteosarcoma
miR-410-3p/HMGB1/NF-κB pathway
Journal
Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521
Informations de publication
Date de publication:
01 Sep 2020
01 Sep 2020
Historique:
received:
28
03
2020
revised:
29
05
2020
accepted:
11
06
2020
pubmed:
20
6
2020
medline:
1
9
2020
entrez:
20
6
2020
Statut:
ppublish
Résumé
Magnoflorine is an essential type of alkaloid and possesses anti-tumor activity in multiple cancers. Recent studies have demonstrated that magnoflorine plays tumor-suppressive roles in gastric and breast cancers. However, its role in osteosarcoma (OS) tumorigenesis is enigmatic. This study aimed to investigate the role and mechanism of magnoflorine in OS. Two human OS cells (MG-63 and U-2 OS) were treated with different concentrations of magnoflorine. Cell viability and invasion were then detected by Cell Counting Kit-8 and Transwell assay, respectively. And the effects of magnoflorine on the epithelial-mesenchymal transition (EMT) and cisplatin sensitivity were also measured. To explore the potential mechanism, we assayed the influence of magnoflorine on the miR-410-3p/HMGB1/NF-κB signaling pathway. Additionally, rescue experiments were performed to further confirm the regulation mechanism of magnoflorine. Magnoflorine inhibited the viability, invasion, and EMT of OS cells in a dose-dependent manner. And it increased the sensitivity of OS cells to cisplatin. Magnoflorine significantly suppressed HMGB1 expression and NF-κB activation, but upregulated miR-410-3p level. Overexpression of HMGB1 promoted NF-κB activation and reversed the effects of magnoflorine on the viability, invasion, EMT and cisplatin sensitivity of OS cells. miR-410-3p mimic inhibited the EMT of OS cells, which was restored by HMGB1 upregulation. And miR-410-3p inhibitor abrogated the influence of magnoflorine on HMGB1 expression in OS cells. Magnoflorine inhibited the malignant phenotypes and increased cisplatin sensitivity of OS cells via modulating miR-410-3p/HMGB1/NF-κB pathway. These results indicated that magnoflorine might be a novel drug for the treatment of OS.
Identifiants
pubmed: 32553931
pii: S0024-3205(20)30717-7
doi: 10.1016/j.lfs.2020.117967
pii:
doi:
Substances chimiques
Aporphines
0
HMGB1 Protein
0
MIRN410 microRNA, human
0
MicroRNAs
0
NF-kappa B
0
magnoflorine
NI8K6962K4
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
117967Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All authors declare no conflicts of interest.