Involvement of the Interferon Signaling Pathways in Pancreatic Cancer Cells.
Aged
Carcinoma in Situ
/ drug therapy
Carcinoma, Pancreatic Ductal
/ drug therapy
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Disease Progression
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Interferons
/ metabolism
Male
Middle Aged
Pancreatic Neoplasms
/ drug therapy
Poly I-C
/ pharmacology
Protein Kinase Inhibitors
/ pharmacology
Sequence Analysis, RNA
Signal Transduction
/ drug effects
Toll-Like Receptors
/ genetics
Interferon
RNA-Seq
TKI
Toll-like receptor
pancreatic cancer
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
04
06
2020
revised:
24
06
2020
accepted:
25
06
2020
entrez:
31
7
2020
pubmed:
31
7
2020
medline:
7
8
2020
Statut:
ppublish
Résumé
To examine interferon (IFN) signaling pathways in human pancreatic cancer cells and their therapeutic application for pancreatic ductal adenocarcinoma (PDAC). We examined the effects of IFNα on cytotoxicity, migration, as well as on the levels of toll-like receptor (TLR) signaling pathway-associated genes expression in pancreatic cancer cells. We also examined the additive effects of IFNα and poly(I-C) on tyrosine kinase inhibitor (TKI)-induced cytotoxicity. We performed transcriptome analysis (RNA-Seq) of clinical samples and compared the profile between pancreatic intraepithelial neoplasias (PanINs) and PDACs. IFNα suppressed cell viability and cell migration, and affected TLR signaling pathways, in pancreatic cancer cells. TLR3 is one of the potential genes involved in IFN-treated pancreatic cancer cells. Furthermore, similar to IFN, extracellular addition of poly(I-C) enhanced TKI-induced cytotoxicity in pancreatic cancer cells. RNA-Seq analysis demonstrated that IFN signaling is one of the potential pathways involved in the progression of PanIN to PDAC. IFN signaling may be involved in the development of PDAC. Treatments that target the IFN and TLR3 signaling pathways may be therapeutic options against PDAC.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
To examine interferon (IFN) signaling pathways in human pancreatic cancer cells and their therapeutic application for pancreatic ductal adenocarcinoma (PDAC).
MATERIALS AND METHODS
METHODS
We examined the effects of IFNα on cytotoxicity, migration, as well as on the levels of toll-like receptor (TLR) signaling pathway-associated genes expression in pancreatic cancer cells. We also examined the additive effects of IFNα and poly(I-C) on tyrosine kinase inhibitor (TKI)-induced cytotoxicity. We performed transcriptome analysis (RNA-Seq) of clinical samples and compared the profile between pancreatic intraepithelial neoplasias (PanINs) and PDACs.
RESULTS
RESULTS
IFNα suppressed cell viability and cell migration, and affected TLR signaling pathways, in pancreatic cancer cells. TLR3 is one of the potential genes involved in IFN-treated pancreatic cancer cells. Furthermore, similar to IFN, extracellular addition of poly(I-C) enhanced TKI-induced cytotoxicity in pancreatic cancer cells. RNA-Seq analysis demonstrated that IFN signaling is one of the potential pathways involved in the progression of PanIN to PDAC.
CONCLUSION
CONCLUSIONS
IFN signaling may be involved in the development of PDAC. Treatments that target the IFN and TLR3 signaling pathways may be therapeutic options against PDAC.
Identifiants
pubmed: 32727774
pii: 40/8/4445
doi: 10.21873/anticanres.14449
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Toll-Like Receptors
0
Interferons
9008-11-1
Poly I-C
O84C90HH2L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4445-4455Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.