Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway

Asian Pac J Cancer Prev. 2019 Dec 1;20(12):3539-3545. doi: 10.31557/APJCP.2019.20.12.3539.

Abstract

Background: Metformin, an antidiabetic drug, has been previously reported to have anti-cancer activities. However, its role in the control of cancer cell migration remains elusive.

Methods: To examine the possible effect of metformin on migration of cervical cancer cells. The related mechanisms were further determined by immunocytochemistry and Western's blotting assay.

Results: The results showed that metformin treatment substantially inhibited the migration ability of cervical cancer cells. Consistently, the filopodia and lamellipodia formation were depleted after exposure to metformin. The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.

Conclusion: Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein. We propose that metformin could be a novel potential candidate as an antimetastatic cancer drug in the cervical cancer management.

Keywords: HeLa; Lamellipodia; Rac1; RhoA; filopodia.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Female
  • Focal Adhesion Kinase 1 / antagonists & inhibitors*
  • HeLa Cells
  • Humans
  • Metformin / pharmacology*
  • Neoplasm Metastasis / drug therapy
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Pseudopodia / drug effects
  • Signal Transduction / drug effects
  • Uterine Cervical Neoplasms / drug therapy*
  • rac1 GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Antineoplastic Agents
  • RAC1 protein, human
  • RHOA protein, human
  • Metformin
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein