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Metformin Induces Resistance of Cancer Cells to the Proteasome Inhibitor Bortezomib

Camille Schlesser1, Thomas Meul1, Georgios Stathopoulos1,2,3

  • 1Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Ludwig-Maximilians University, Max-Lebsche Platz 31, 81377 Munich, Germany.

Biomolecules
|June 24, 2022
PubMed

Insights

Metformin impairs proteasome function, leading to cancer cell resistance against proteasome inhibitors like Bortezomib. This interaction is crucial for understanding cancer treatment efficacy.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Metformin, an anti-diabetic drug, is under investigation for cancer treatment.
  • Proteasome inhibitors, such as Bortezomib, are approved for certain hematological cancers and studied for lung cancer.

Purpose of the Study:

  • To analyze the interaction between metformin and Bortezomib in mantle cell lymphoma and non-small-cell lung cancer cells.
  • To investigate the impact of metformin on proteasome activity and its implications for proteasome inhibitor therapy.

Main Methods:

  • Proliferation and survival assays were conducted on Jeko-1 and H1299 cancer cell lines.
  • Native-gel electrophoresis was used to assess proteasome activity and assembly.
  • Expression analysis of proteasome assembly factors was performed.

Main Results:

  • Metformin treatment resulted in impaired 26S proteasome activity and assembly in cancer cells.
  • Metformin induced resistance to Bortezomib in both mantle cell lymphoma and non-small-cell lung cancer cell lines.
  • The drug's effects on proteasome function were linked to alterations in proteasome assembly factors.

Conclusions:

  • Metformin compromises proteasome complex integrity and function.
  • This impairment confers resistance to proteasome inhibitors, potentially affecting therapeutic outcomes.
  • Findings highlight the importance of considering metformin's effects in patients undergoing proteasome inhibitor therapy.
Keywords:
26S proteasomemetforminproteasome activityproteasome inhibitorresistance

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