Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells

Dis Markers. 2022 Jun 24:2022:5709259. doi: 10.1155/2022/5709259. eCollection 2022.

Abstract

Background: Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients.

Methods: Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting.

Results: Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins.

Conclusion: The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Phthalazines
  • Piperazines
  • Proto-Oncogene Proteins c-myc
  • Signal Transduction
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Phthalazines
  • Piperazines
  • Proto-Oncogene Proteins c-myc
  • Metformin
  • olaparib