Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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Antitumor Effect of Metformin in Combination with Binimetinib on Melanoma Cells

  • Lee, Eunsung (Department of Medicine, Jeju National University College of Medicine) ;
  • Kwon, Yongjae (Department of Medicine, Jeju National University College of Medicine) ;
  • Kim, Jiwon (Department of Medicine, Jeju National University College of Medicine) ;
  • Park, Deokbae (Department of Histology, Jeju National University College of Medicine) ;
  • Lee, Youngki (Department of Histology, Jeju National University College of Medicine)
  • Received : 2021.03.26
  • Accepted : 2021.05.20
  • Published : 2021.06.30
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Abstract

Cutaneous melanoma is a fatal disease for patients with distant metastasis. Metformin is the most widely used anti-diabetic drug, and proved to suppress cell proliferation and metastasis in diverse cancers including melanoma. We previously reported that MEK inhibitor trametinib increases the expression of epithelial-mesenchymal transition (EMT) regulators and melanoma cell motility, which are suppressed by addition of metformin in A375 melanoma cells. To confirm our findings further, we first evaluated the effect of metformin in combination with another MEK inhibitor binimetinib on cell viability in G361 melanoma cells. We then investigated whether binimetinib affects the expression of EMT regulators and cell motility. We finally monitored the effect of metformin on binimetinib-induced cell migration. Cell viability assay showed that combination index (CI) value at ED50 is 0.80, suggesting synergy for the combination of metformin with binimetinib. Our results also revealed that binimetinib increased the expression of EMT regulators such as integrin αV, fibronectin and slug, which correlate well with the enhanced cell migration in wound healing assay. Metformin, on the contrary, suppressed the expression of sparc, integrin αV, fibronectin and N-cadherin with the reduced cell motility. The combination treatment showed that metformin counteracts the binimetinib-induced increase of cell motility. Overall, these results suggest that metformin with binimetinib might be useful as a potential therapeutic adjuvant against cell survival and metastatic activity in melanoma patients.

Keywords

Acknowledgement

This research was supported by the 2020 scientific promotion program funded by Jeju National University.

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