Effects of pirfenidone targeting the tumor microenvironment and tumor-stroma interaction as a novel treatment for non-small cell lung cancer.

Abstract:

:Targeting cancer-associated fibroblasts (CAFs), as well as the crosstalk between stroma and cancer cells, could be of value in managing cancers. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis. This study aimed to investigate the possibility that PFD might exert an anti-tumor effect through inhibition of fibroblast activation and the tumor-stroma interaction in non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. PFD significantly inhibited myofibroblast differentiation and activation of both primary cultured normal human lung fibroblasts and CAFs. Cocultivation of NSCLC cells with conditioned media (CM) of fibroblasts changed the morphology or epithelial to mesenchymal transition (EMT) status, and PFD suppressed these changes. Cocultivation of CAFs with CM of NSCLC cells also induced activation of CAFs, and these changes were suppressed by PFD. On in vivo examination, CAFs promoted tumor progression, and PFD suppressed tumor progression with an inhibitory effect on tumor-stroma crosstalk. PFD might inhibit not only fibroblast activity, but also the crosstalk between cancer cells and fibroblasts. PFD may have great potential as a novel treatment for NSCLC from multiple perspectives.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Fujiwara A,Funaki S,Fukui E,Kimura K,Kanou T,Ose N,Minami M,Shintani Y

doi

10.1038/s41598-020-67904-8

subject

Has Abstract

pub_date

2020-07-02 00:00:00

pages

10900

issue

1

issn

2045-2322

pii

10.1038/s41598-020-67904-8

journal_volume

10

pub_type

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