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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Sci+Rep
2018 ; 8
(1
): 10070
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Pirfenidone decreases mesothelioma cell proliferation and migration via
inhibition of ERK and AKT and regulates mesothelioma tumor microenvironment in
vivo
#MMPMID29968778
Li C
; Rezov V
; Joensuu E
; Vartiainen V
; Rönty M
; Yin M
; Myllärniemi M
; Koli K
Sci Rep
2018[Jul]; 8
(1
): 10070
PMID29968778
show ga
Malignant mesothelioma is an aggressive cancer with poor prognosis. It is
characterized by prominent extracellular matrix, mesenchymal tumor cell
phenotypes and chemoresistance. In this study, the ability of pirfenidone to
alter mesothelioma cell proliferation and migration as well as mesothelioma tumor
microenvironment was evaluated. Pirfenidone is an anti-fibrotic drug used in the
treatment of idiopathic pulmonary fibrosis and has also anti-proliferative
activities. Mesothelioma cell proliferation was decreased by pirfenidone alone or
in combination with cisplatin. Pirfenidone also decreased significantly Transwell
migration/invasion and 3D collagen invasion. This was associated with increased
BMP pathway activity, decreased GREM1 expression and downregulation of MAPK/ERK
and AKT/mTOR signaling. The canonical Smad-mediated TGF-? signaling was not
affected by pirfenidone. However, pirfenidone blocked TGF-? induced upregulation
of ERK and AKT pathways. Treatment of mice harboring mesothelioma xenografts with
pirfenidone alone did not reduce tumor proliferation in vivo. However,
pirfenidone modified the tumor microenvironment by reducing the expression of
extracellular matrix associated genes. In addition, GREM1 expression was
downregulated by pirfenidone in vivo. By reducing two major upregulated pathways
in mesothelioma and by targeting tumor cells and the microenvironment pirfenidone
may present a novel anti-fibrotic and anti-cancer adjuvant therapy for
mesothelioma.