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Antifibrotic Agent Pirfenidone Suppresses Proliferation of Human Pancreatic Cancer Cells by Inducing G0/G1 Cell Cycle Arrest

Background: Pirfenidone (PFD), which is an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis, induces G0/G1 cell cycle arrest in fibroblasts. We hypothesized that PFD-induced G0/G1 cell cycle arrest might be achieved in other types of cells, including cancer cells. Here we investigated the effects of PFD on the proliferation of pancreatic cancer cells (PCCs) in vitro. Method: Human skin fibroblasts ASF-4-1 cells and human prostate stromal cells (PrSC) were used as fibroblasts. PANC-1, MIA PaCa-2, and BxPC-3 cells were used as human PCCs. Cell cycle and apoptosis were analyzed using flow cytometer. Results: First, we confirmed that PFD suppressed cell proliferation of ASF-4-1 cells and PrSC and induced G0/G1 cell cycle arrest. Under these experimental conditions, PFD also suppressed cell proliferation and induced G0/G1 cell cycle arrest in all PCCs. In PFD-treated PCCs, expression of p21 was increased but that of CDK2 was not clearly decreased. Of note, PFD did not induce significant apoptosis among PCCs. Conclusions: These results demonstrated that the antifibrotic agent PFD might have antiproliferative effects on PCCs by inducing G0/G1 cell cycle arrest. This suggests that PFD may target not only fibroblasts but also PCCs in the tumor microenvironment of pancreatic cancer.