Mesothelioma xenografts in nude mice: PBS treated versus pirfenidone treated

Background: 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. Aims: Transcriptional profiling using RNA sequencing of human mesothelioma xenograft tumors treated with PBS or pirfenidone. Aim was to compare extracellular matrix and fibrosis related genes. Results: 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. Conclusion: 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. Two condition experiment, PBS treated (CTRL) 3 replicates and pirfenidone treated (PFD) 5 replicates