Roles of metformin-mediated girdin expression in metastasis of epithelial ovarian cancer

Cell Biol Int. 2021 May;45(5):1030-1037. doi: 10.1002/cbin.11547. Epub 2021 Jan 21.

Abstract

Antimetastatic effect of Metformin has been documented in epithelial ovarian cancer (EOC). Presently, we investigated the regulatory mechanism of Metformin in EOC metastasis. First, Girdin was significantly enhanced in EOC tumorous tissues and cell lines. Seconded, knockdown of Girdin significantly suppressed EOC cell viability, migration, and invasion, while upregulation of Girdin produced the opposite effects in vitro and facilitated lung metastasis in EOC cell xenograft in vivo. In addition, we confirmed that the inhibitory effect of Metformin on Girdin expression. Mechanistically, the oncogenic effects of Girdin could be reversed by LY294002 (an AKT pathway inhibitor) and Metformin. These results suggested that Metformin attenuated EOC metastasis through Girdin and targeting Girdin may be a promising therapeutic strategy for EOC in the future.

Keywords: Girdin; Metformin; epithelial ovarian cancer (EOC); metastasis.

MeSH terms

  • Adult
  • Animals
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism*
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Metformin / metabolism
  • Metformin / pharmacology
  • Mice
  • Mice, Nude
  • Microfilament Proteins / drug effects
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / drug therapy*
  • Neoplasm Metastasis / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Transcriptome / genetics
  • Vesicular Transport Proteins / drug effects
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism

Substances

  • CCDC88A protein, human
  • Microfilament Proteins
  • Vesicular Transport Proteins
  • Metformin