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

  • Biosci Biotechnol Biochem. 2026 Jun 23;90(7):877-885. doi: 10.1093/bbb/zbag054.
Zehai Xia  1 ,  Quan Wang  2 ,  Lei Zheng  2 ,  Qun Lv  1
Affiliations
  • 1. Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China.
  • 2. Clinical Medical College, Hangzhou Normal University, Hangzhou, Zhejiang, China.
PMID: 42012458 DOI: 10.1093/bbb/zbag054
Abstract

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.

Keywords
autophagy; lung cancer; lymph angiogenesis; pirfenidone; polo-like kinase 1.
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