Irisin/FNDC5 inhibits the epithelial-mesenchymal transition of epithelial ovarian cancer cells via the PI3K/Akt pathway

Arch Gynecol Obstet. 2022 Sep;306(3):841-850. doi: 10.1007/s00404-022-06427-1. Epub 2022 Feb 14.

Abstract

Purpose: This study explored the role of irisin/fibronectin type III domain-containing protein 5 (FNDC5) in epithelial ovarian cancer and investigated its underlying mechanisms.

Methods: Immunohistochemistry was performed to analyze the expression of irisin/FNDC5 in epithelial ovarian cancer and normal ovarian tissues. Cell Counting Kit-8, transwell, and wound-healing assays were performed to examine the effect of irisin on the viability, migration, and invasion of ovarian cancer cells, respectively. Western blotting was used to detect the changes of epithelial-mesenchymal transition (EMT)-related proteins and phosphatidylinositol 3-kinase (PI3K)/Akt pathway proteins. Ovarian cancer cells were treated in vitro with the PI3K agonist (740Y-P) in combination with irisin to explore the mechanism of irisin in ovarian cancer.

Results: The expression of irisin/FNDC5 in epithelial ovarian cancer tissue was significantly higher than that in normal ovarian tissues, and the expression in late stage patients with lymph node metastasis was lower than that in early stage patients without metastasis. Irisin inhibited the proliferation, invasion, and migration of epithelial ovarian cancer cells, down-regulated phosphorylated Akt, and inhibited EMT progression. The PI3K agonist, 740Y-P, partially reversed the effects of irisin on the invasion, migration, and EMT of ovarian cancer cells.

Conclusion: These findings show that irisin/FNDC5 was highly expressed in ovarian cancer tissues, which may regulate the EMT through the PI3K/Akt signaling pathway and inhibit the proliferation, invasion, and migration of epithelial ovarian cancer.

Keywords: Cell invasion; EMT; Epithelial ovarian cancer; Irisin/FNDC5; PI3K/Akt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Fibronectins / metabolism
  • Humans
  • Ovarian Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinase / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Transcription Factors

Substances

  • FNDC5 protein, human
  • Fibronectins
  • Transcription Factors
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt