Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal interstitial lung disease. Actually, no treatment can block or reverse the development of lung fibrosis in patients suffering from IPF. The discovery of new antifibrosing drugs remains thus an area of intensive research. Arsenic trioxide (ATO), a safe and effective pro-oxidant drug used in cancer therapy, reduces in vivo experimental pulmonary fibrosis and prevents in vitro the differentiation of normal human lung fibroblasts (HLFs). In this context, the goal of this study was to determine if ATO could inhibit the main functions of HLFs isolated from patients with IPF.

IPF and non-IPF HLFs derived from lung biopsy isolated from patients with IPF or primary lung cancer. After pre-treatment with ATO (0.01–1μM) and stimulation with PDGF-BB (50ng/ml) or TGF-β1 (1ng/ml), proliferation, migration and differentiation of HLFs were assessed as well as the cell stress response.

ATO did not affect cell viability but it significantly decreased, in a concentration-dependent manner, the proliferation and migration of control and IPF HLFs induced by PDGF-BB. The metalloid also prevented the myofibroblastic differentiation of HLFs determined by the expression of α-smooth muscle actin (α-SMA) and Collagen-1 proteins and the phosphorylation of SMAD2/3 in TGF-β1-stimulated HLFs. ATO effects were associated with stabilization of the transcription factor NRF2 and induction of the antioxidant proteins NQO1 and HO-1 that emphases the stress response developed by ATO-treated HLFs.

Our results demonstrate that ATO, in the range of arsenic plasmatic levels measured in patients treated with standard dosing of this drug, counteracted in vitro the detrimental functions of HLFs isolated from patients with IPF. ATO may thus be taken into consideration in the future as a new therapeutic option for IPF treatment.