Metformin Inhibits Cell Motility and Proliferation of Triple-Negative Breast Cancer Cells by Blocking HMGB1/RAGE...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• High-mobility group box 1 (HMGB1) is a nuclear protein implicated in tumor progression and metastasis.
• The HMGB1/receptor for advanced glycation end products (RAGE) axis promotes aggressive cancer phenotypes.
• Metformin, an antidiabetic drug, has shown potential in modulating inflammatory pathways.

Purpose of the Study:

• To investigate the effects of metformin on the HMGB1/RAGE signaling pathway in triple-negative breast cancer (TNBC).
• To evaluate metformin's impact on TNBC cell migration, proliferation, and metastasis-associated molecular mechanisms.

Main Methods:

• Wound-healing and colony formation assays were used to assess cell migration and proliferation.
• Immunoblotting and immunofluorescence analyses were performed to examine protein expression and localization.
• Key signaling molecules including RAGE, NF-κB, E-cadherin, vimentin, and β-catenin were analyzed.

Main Results:

• Metformin significantly reduced HMGB1-induced migration and proliferation in TNBC cells.
• Metformin decreased RAGE stabilization, disrupted NF-κB signaling, and reversed epithelial-to-mesenchymal transition (EMT).
• Metformin treatment led to decreased HMGB1 and RAGE protein levels, disrupting a pro-metastatic feedback loop.

Conclusions:

• Metformin effectively inhibits the HMGB1/RAGE signaling pathway in TNBC.
• Metformin demonstrates therapeutic potential for TNBC by suppressing metastasis.
• Targeting the HMGB1/RAGE pathway with metformin offers a novel strategy for aggressive cancer treatment.