The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-κB pathways

J Int Med Res. 2020 Jun;48(6):300060520925996. doi: 10.1177/0300060520925996.

Abstract

Objective: Disulfiram is commonly used for alcohol abuse; however, recent studies have revealed its potential as an anti-cancer treatment. This study investigated the effects of disulfiram on gastric cancer and its underlying mechanisms of action.

Methods: The gastric cancer cell lines MKN-45 and SGC-7901 were used for all experiments. Cell proliferation was investigated using cell counting kit-8, cell migration and invasion were examined using Transwell assays, the proliferation and metastasis related proteins PCNA and MMP-2, respectively, were detected by ELISA. To explore the underlying molecular mechanisms, we also examined levels of proteins involved in the Wnt and NF-κB pathways by ELISA.

Results: Disulfiram significantly inhibited the proliferation, migration, and invasion of gastric cancer cells and decreased PCNA and MMP-2 levels. Additionally, disulfiram-treated MKN-45 and SGC-7901 cells showed reduced expression of Wnt, β-catenin, and NF-κB.

Conclusion: Disulfiram regulates the Wnt and NF-κB pathways, and thus could be a potential treatment for managing gastric cancer.

Keywords: Disulfiram; NF-kB; Wnt; cancer stem cell; gastric cancer; β-catenin.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Progression
  • Disulfiram / pharmacology*
  • Disulfiram / therapeutic use
  • Drug Repositioning
  • Drug Screening Assays, Antitumor
  • Humans
  • NF-kappa B / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Wnt Signaling Pathway / drug effects

Substances

  • NF-kappa B
  • Disulfiram