Inhibitory effect of cathepsin K inhibitor (ODN-MK-0822) on invasion, migration and adhesion of human breast cancer cells in vitro.
Benzamides
/ pharmacology
Biphenyl Compounds
/ pharmacology
Breast Neoplasms
/ drug therapy
Cathepsin K
/ antagonists & inhibitors
Cell Adhesion
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Matrix Metalloproteinase 9
/ genetics
Neoplasm Invasiveness
/ genetics
Neoplasm Metastasis
Neoplasm Proteins
/ genetics
Organic Chemicals
/ pharmacology
Phosphatidylinositol 3-Kinases
/ genetics
Piperazines
/ pharmacology
Tissue Inhibitor of Metalloproteinase-1
/ genetics
Adhesion
Breast cancer
Cathepsin K
Invasion
Migration
Odanacatib
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
16
06
2020
accepted:
23
10
2020
pubmed:
10
12
2020
medline:
26
5
2021
entrez:
9
12
2020
Statut:
ppublish
Résumé
Approximately 90% of patients with advanced breast cancer develop bone metastases; an event that results in severe decrease of quality of life and a drastic deterioration in prognosis. Therefore, to increase the survival of breast cancer patients, the development of new therapeutic strategies to impair metastatic process and skeletal complications is critical. Previous studies on the role of cathepsin K (CTSK) in metastatic spreading led to several strategies for inhibition of this molecule such as MIV-711 (Medivir), balicatib and odanacatib (ODN) which were on trial in the past. The present study intended to assess the anti-metastatic efficacy of ODN in breast cancer cells. Human breast cancer cell lines MDA-MB-231 were treated with different concentrations of ODN and performed invasion, adhesion and migration assays and, RT-PCR and western blot to evaluate the effect of ODN on the metastatic potential of breast cancer cells. ODN markedly decreased wound healing cell migration, invasion and adhesion at a dose dependent manner. ODN inhibits cell invasion by decreasing the matrix metalloproteinase (MMP-9) with the upregulation of TIMP-1 expression. ODN effectively inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal Kinase (JNK), and blocked the expression of β-integrins and FAK proteins. ODN also significantly inhibited PI3K downstream targets Rac1, Cdc42, paxillin and Src which are critical for cell adhesion, migration and cytoskeletal reorganization. ODN exerts anti-metastatic action through inhibition of signaling pathway for MMP-9, PI3K and MAPK. This indicates potential therapeutic effects of ODN in the treatment of metastatic breast cancer.
Identifiants
pubmed: 33294960
doi: 10.1007/s11033-020-05951-0
pii: 10.1007/s11033-020-05951-0
doi:
Substances chimiques
Benzamides
0
Biphenyl Compounds
0
MIV-711
0
Neoplasm Proteins
0
Organic Chemicals
0
Piperazines
0
Tissue Inhibitor of Metalloproteinase-1
0
balicatib
E00MVC7O57
Cathepsin K
EC 3.4.22.38
Matrix Metalloproteinase 9
EC 3.4.24.35
odanacatib
N673F6W2VH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105-116Subventions
Organisme : UGC:NFST
ID : NFST-2015-17-ST-MAN-689
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