TrkB/BDNF Signaling Could Be a New Therapeutic Target for Pancreatic Cancer.
Brain-Derived Neurotrophic Factor
/ genetics
Carbazoles
/ pharmacology
Carcinoma, Pancreatic Ductal
/ metabolism
Cell Line, Tumor
Cell Proliferation
/ drug effects
Humans
Indole Alkaloids
/ pharmacology
Membrane Glycoproteins
/ antagonists & inhibitors
Pancreatic Neoplasms
/ metabolism
Protein Kinase Inhibitors
/ pharmacology
RNA Interference
RNA, Small Interfering
/ genetics
Receptor, trkB
/ antagonists & inhibitors
Signal Transduction
/ drug effects
BDNF
TrkB
invasion
pancreatic cancer
proliferation
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
22
05
2021
revised:
28
06
2021
accepted:
29
06
2021
entrez:
20
7
2021
pubmed:
21
7
2021
medline:
30
7
2021
Statut:
ppublish
Résumé
Tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling plays a role in inducing malignant phenotypes in several aggressive types of cancers. To create a conclusive therapy targeting TrkB/BDNF signaling in solid refractory cancers, the biological significance of TrkB/BDNF signaling was analyzed in pancreatic ductal adenocarcinoma (PDAC) cells. Three PDAC cell lines were used as target cells to investigate proliferation and invasiveness. Small interfering RNA (siRNA) and the TrkB tyrosine kinase inhibitor k252a were used as TrkB/BDNF signaling inhibitors. All PDAC cell lines expressed TrkB and BDNF. When TrkB and BDNF were inhibited by siRNA or k252a, the invasiveness of PANC-1 and SUIT-2 cells significantly decreased. When TrkB was inhibited by siRNA or k252a, proliferation was significantly inhibited in PDAC cells. TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling plays a role in inducing malignant phenotypes in several aggressive types of cancers. To create a conclusive therapy targeting TrkB/BDNF signaling in solid refractory cancers, the biological significance of TrkB/BDNF signaling was analyzed in pancreatic ductal adenocarcinoma (PDAC) cells.
MATERIALS AND METHODS
METHODS
Three PDAC cell lines were used as target cells to investigate proliferation and invasiveness. Small interfering RNA (siRNA) and the TrkB tyrosine kinase inhibitor k252a were used as TrkB/BDNF signaling inhibitors.
RESULTS
RESULTS
All PDAC cell lines expressed TrkB and BDNF. When TrkB and BDNF were inhibited by siRNA or k252a, the invasiveness of PANC-1 and SUIT-2 cells significantly decreased. When TrkB was inhibited by siRNA or k252a, proliferation was significantly inhibited in PDAC cells.
CONCLUSION
CONCLUSIONS
TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.
Identifiants
pubmed: 34281873
pii: 41/8/4047
doi: 10.21873/anticanres.15205
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Carbazoles
0
Indole Alkaloids
0
Membrane Glycoproteins
0
Protein Kinase Inhibitors
0
RNA, Small Interfering
0
BDNF protein, human
7171WSG8A2
staurosporine aglycone
97161-97-2
Receptor, trkB
EC 2.7.10.1
tropomyosin-related kinase-B, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4047-4052Informations de copyright
Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.