The Multi-Modal Effect of the Anti-fibrotic Drug Pirfenidone on NSCLC.
SMAD
TGFβ
immunotherapy
lung cancer
tumor microenvironment
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2019
2019
Historique:
received:
30
09
2019
accepted:
20
12
2019
entrez:
11
2
2020
pubmed:
11
2
2020
medline:
11
2
2020
Statut:
epublish
Résumé
Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the
Identifiants
pubmed: 32039023
doi: 10.3389/fonc.2019.01550
pmc: PMC6985561
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1550Informations de copyright
Copyright © 2020 Marwitz, Turkowski, Nitschkowski, Weigert, Brandenburg, Reiling, Thomas, Reck, Drömann, Seeger, Rabe, Savai and Goldmann.
Références
Eur Respir Rev. 2011 Jun;20(120):85-97
pubmed: 21632796
Med Sci Monit. 2017 Dec 25;23:6107-6113
pubmed: 29276937
Cancer Lett. 2007 Apr 28;249(1):49-60
pubmed: 17275177
Respir Investig. 2018 Jan;56(1):72-79
pubmed: 29325685
Cell Signal. 2020 Jan;65:109432
pubmed: 31693876
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Biochem Biophys Res Commun. 2015 Jun 26;462(2):138-43
pubmed: 25935484
Expert Opin Investig Drugs. 2010 Feb;19(2):275-83
pubmed: 20050822
Ann Oncol. 2018 Oct 1;29(Suppl 4):iv192-iv237
pubmed: 30285222
Nat Commun. 2018 Nov 8;9(1):4692
pubmed: 30410077
Oncoimmunology. 2017 Jul 13;6(10):e1349589
pubmed: 29123964
Oncotarget. 2017 Apr 11;8(15):24506-24517
pubmed: 28445938
Nature. 2018 Feb 22;554(7693):544-548
pubmed: 29443960
Respir Res. 2014 Feb 08;15:16
pubmed: 24507087
Pharmacology. 2019;103(5-6):250-256
pubmed: 30731453
Biomed Pharmacother. 2018 Apr;100:233-239
pubmed: 29432994
J Cell Sci. 2002 Dec 1;115(Pt 23):4555-64
pubmed: 12415000
N Engl J Med. 2014 May 29;370(22):2083-92
pubmed: 24836312
N Engl J Med. 2017 Aug 31;377(9):849-861
pubmed: 28854088
Eur Respir J. 2009 Jan;33(1):127-33
pubmed: 18715879
PLoS One. 2018 Nov 27;13(11):e0207915
pubmed: 30481203
Nat Commun. 2019 Apr 18;10(1):1812
pubmed: 31000705
Cancer Discov. 2016 Dec;6(12):1366-1381
pubmed: 27683557
Cancer Res. 2016 Jul 1;76(13):3785-801
pubmed: 27197161
Am J Respir Cell Mol Biol. 2017 May;56(5):667-679
pubmed: 28459387
Sci Rep. 2018 Feb 13;8(1):2918
pubmed: 29440769
Nature. 2018 Feb 22;554(7693):538-543
pubmed: 29443964
PLoS One. 2011;6(5):e20319
pubmed: 21625455
Sci Rep. 2018 Jul 3;8(1):10070
pubmed: 29968778
Oncogene. 2015 Mar 19;34(12):1487-98
pubmed: 24704832
BMC Cancer. 2016 Mar 02;16:176
pubmed: 26935219
Proc Am Thorac Soc. 2012 Jul;9(3):111-6
pubmed: 22802283
Oncoimmunology. 2018 Feb 14;7(5):e1426519
pubmed: 29721396
Respir Res. 2019 Oct 23;20(1):230
pubmed: 31647033
J Thorac Oncol. 2010 Jan;5(1):29-33
pubmed: 19952801
BMC Pulm Med. 2012 Jun 13;12:24
pubmed: 22694981
Oncotarget. 2016 Dec 13;7(50):82889-82901
pubmed: 27756881
Clin Cancer Res. 2006 Jan 15;12(2):405-10
pubmed: 16428479