Effect of pirfenidone on the regulation of lymph angiogenesis by PLK1 signaling to inhibit metastasis of lung cancer <i>in vivo</i>

This study investigated the mechanism of pirfenidone (PFD) inhibiting metastasis of lung cancer in vivo.A nude mouse lung cancer model was established and treated with PFD (200, 400 μg/mL); lung metastatic tumor weight was recorded, Lyve-1 (lymphatic marker), LC3II (autophagy protein) and polo-like kinase 1 (PLK1) were detected. In human lung lymphatic endothelial cells (HMVEC-LLy) cells, 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 down-regulated the expression levels of Lyve-1, LC3II/LC3I and PLK1. In cell experiments, PFD was found to inhibit HMVEC-LLy migration, apoptosis and lymph angiogenesis, as well as down-regulate 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 lymph angiogenesis through PLK1 signaling.