Effect of pirfenidone on the regulation of lymph angiogenesis by PLK1 signaling to inhibit metastasis of lung cancer in vivo.

This study investigated the mechanism of pirfenidone (PFD) inhibiting the metastasis of lung cancer in vivo. A nude mouse lung cancer model was established and treated with PFD (200 and 400 mg/kg); lung metastatic tumor weight was recorded, Lyve-1 (lymphatic marker), LC3I and LC3II (autophagy protein), and polo-like kinase 1 (PLK1) were detected. In human lung lymphatic endothelial cells (HMVEC-LLy), PFD's effects on migration, apoptosis, lymphangiogenesis, and LC3II/LC3I/PLK1 levels were tested. PLK1-overexpressed HMVEC-LLy cells were treated with 400 μg/mL PFD to explore its mechanism. PFD inhibited the weight of lung metastases and downregulated the expression levels of Lyve-1, LC3II/LC3I, and PLK1. In cell experiments, PFD was found to inhibit HMVEC-LLy migration and lymph angiogenesis, and promote apoptosis, as well as downregulate LC3II/LC3I and PLK1 protein levels, and these effects could be reversed by PLK1 overexpression. PFD may inhibit lung cancer metastasis in vivo by regulating lymphangiogenesis through PLK1 signaling.