Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts

Conte, Enrico; Gili, Elisa; Fagone, Evelina; Fruciano, Mary; Iemmolo, Maria; Vancheri, Carlo

doi:10.1016/j.ejps.2014.02.014

Cited by 298 publications

(227 citation statements)

References 30 publications

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“…Previous studies have demonstrated that pirfenidone is able to suppress the differentiation of several cell types (24)(25)(26)(27)(28). Conte et al (24) reported that pirfenidone reduced fibroblast proliferation, attenuated TGF-β-induced α-smooth muscle actin and inhibited the TGF-β-induced phosphorylation of Smad3 in human lung fibroblast cells.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma

et al. 2017

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Abstract. The epithelial-to-mesenchymal transition (EMT) in cancer is associated with invasion, metastasis and chemoresistance. Recent studies have revealed the increased expression of programmed death-ligand 1 (PD-L1) in cells undergoing EMT. The underlying mechanism of EMT involves transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2). Pirfenidone and the known EMT-suppressor nintedanib suppress pulmonary fibrosis partially through suppression of TGF-β. The present study aimed to determine whether pirfenidone has the potential to induce EMT-reversion, using nintedanib as a reference. The human lung adenocarcinoma cell lines A-549, HCC-827, and PC-9 were treated with TGF-β and FGF-2 to induce EMT. The EMT-induced cells were further treated with pirfenidone or nintedanib. Phenotypic alterations associated with EMT were assessed by examining the following: i) The expression levels of E-cadherin, vimentin, fibronectin and slug, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescent immunohistochemistry; ii) cell motility via wound-healing assays; and iii) the expression of PD-L1 using RT-qPCR. The combination of TGF-β and FGF-2 successfully induced EMT in all three cell lines, characterized by a significant reduction in E-cadherin expression in the A-549 and HCC-827 cells, increased expression levels of vimentin, fibronectin, slug and PD-L1, and increased cell motility in all three cell lines. Pirfenidone and nintedanib reverted all of these phenotypes, with the exception of unaltered E-cadherin expression in all three cell lines, and inconsistent expression of vimentin in the HCC-827 and PC-9 cells. Thus, pirfenidone and nintedanib have the ability to induce EMT-reversion in human lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma

et al. 2017

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“…In vitro, pirfenidone inhibited the TGF-β1-induced differentiation of human lung fibroblasts into myofibroblasts and thereby prevented the excessive synthesis of collagen [24].…”

Section: Resultsmentioning

confidence: 99%

Reduction of Postoperative Adhesions after Laparoscopic Surgery for Endometriosis by Using a Novel Anti-Fibrotic Drug Pirfenidone: A Randomized Double Blind Study

El-Halwagy¹,

Al-Gergawy²,

Dawood³

et al. 2017

Gynecol Obstet

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“…[31] The drug works by reducing fibroblast proliferation, TGF-beta induced alpha-smooth muscle actin, pro-collagen mRNA, and protein. [32] The use of pirfenidone could theoretically reduce the fibrosis associated with PDAC as well as improve chemotherapy penetration.…”

Section: Drug Name Mechanism Of Action Referencementioning

confidence: 99%

“…Olmesartan Reduce collagen deposition and reduce activation of alpha-smooth muscle actin [29] Non-anticoagulant low molecular weight heparin (S-NACH) Mechanism unknown, but has shown improved chemo uptake into the tumor [30] Pirfenidone Reduces fibroblast production, alpha-smooth muscle actin, pro-collagen mRNA, and proteins; not yet studied in pancreatic cancer [32] PEGPH20 Depletes hyaluronan, an extracellular matrix tumor component; results in normalized interstitial fluid pressure and improved drug delivery [33,34] Another novel idea for reducing PDAC fibrosis could involve experimental treatment with a new antifibrotic agent called pirfenidone. While the agent has only been FDAapproved to treat idiopathic pulmonary fibrosis, the mechanism of action should translate successfully in the treatment of PDAC.…”

Section: Drug Name Mechanism Of Action Referencementioning

confidence: 99%

Emerging therapies for pancreatic ductal carcinoma

Falcone

Davis

Stain

et al. 2016

JST

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Pancreatic ductal adenocarcinoma (PDAC) is a solid tumor mass that grows and metastasizes rapidly. There are no definitive methods for early detection and most patients are diagnosed at a late stage. Those diagnosed at an early stage are eligible for tumor resection. However, many of these patients are soon burdened with tumor recurrence. The tumor grows back aggressively and with resistance to the original chemotherapy. Gemcitabine has been the treatment of choice, but provides only minimal survival prolongation. Researchers are trying to improve the current standard of care by finding different methods to improve treatment efficacy and reduce side effects. This review emphasizes recent data on targeting the tumor using antifibrotic, nanotargeted, and dendritic cell therapies. Antifibrotic therapy aims to reduce tumor fibrosis, which prevents adequate chemotherapy penetration. Nanotargeted therapy offers precise targeting of cancer cells and chemotherapy delivery. Dendritic cell vaccines stimulate the body's immune system to target PDAC cells. These three treatment methods or a combination of them might improve the lifespan and quality of life for PDAC patients.

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Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts

Cited by 298 publications

References 30 publications

Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma

Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma

Reduction of Postoperative Adhesions after Laparoscopic Surgery for Endometriosis by Using a Novel Anti-Fibrotic Drug Pirfenidone: A Randomized Double Blind Study

Emerging therapies for pancreatic ductal carcinoma

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