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2018 ; 4
(ä): 17
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2-aminopurine suppresses the TGF-?1-induced epithelial-mesenchymal transition and
attenuates bleomycin-induced pulmonary fibrosis
#MMPMID29531814
Weng D
; Chen JX
; Li HH
; Liu F
; Zhou LD
; Liu HP
; Zheng RJ
; Jiang Y
; Liu ZH
; Ge B
Cell Death Discov
2018[Dec]; 4
(ä): 17
PMID29531814
show ga
The epithelial-mesenchymal transition (EMT) is a multifunctional cell process
involved in the pathogenesis of numerous conditions, including fibrosis and
cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease
characterized by fibroblast accumulation and collagen deposition in the lungs.
The fibroblasts involved in this process partially originate from lung epithelial
cells via the EMT. Evidence suggests that the EMT contributes to progression,
invasion, and metastasis of various types of cancer. We screened a series of 80
compounds for the ability to interfere with the EMT and potentially be applied as
a therapeutic for IPF and/or lung cancer. We identified 2-aminopurine (2-AP), a
fluorescent analog of guanosine and adenosine, as a candidate in this screen.
Herein, we demonstrate that 2-AP can restore E-cadherin expression and inhibit
fibronectin and vimentin expression in TGF-?1-treated A549 lung cancer cells.
Moreover, 2-AP can inhibit TGF-?1-induced metastasis of A549 cells. This compound
significantly attenuated bleomycin (BLM)-induced pulmonary inflammation, the EMT,
and fibrosis. In addition, 2-AP treatment significantly decreased mortality in a
mouse model of pulmonary fibrosis. Collectively, we determined that 2-AP could
inhibit metastasis in vitro by suppressing the TGF-?1-induced EMT and could
attenuate BLM-induced pulmonary fibrosis in vivo. Results of this study suggest
that 2-AP may have utility as a treatment for lung cancer and pulmonary fibrosis.