Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models

Area of Science:

• Oncology
• Pharmacology
• Drug Discovery

Background:

• Drug discovery for cancer is costly and inefficient.
• Drug repositioning offers a viable alternative strategy.
• Triple-negative breast cancer (TNBC) remains a challenging subtype requiring novel therapeutic approaches.

Purpose of the Study:

• To evaluate the antitumor efficacy of a combination therapy using two repositioned drugs, metformin and propranolol.
• To assess the effects of this combination on TNBC cell proliferation, mitochondrial activity, migration, and invasion.
• To investigate the in vivo efficacy of metformin and propranolol in reducing tumor growth and metastasis in TNBC models.

Main Methods:

• In vitro studies using five distinct breast cancer cell lines.
• In vivo studies utilizing immunocompetent mouse models of TNBC.
• Metronomic drug administration protocol for combined metformin and propranolol treatment.

Main Results:

• Combined metformin and propranolol significantly decreased cancer cell proliferation, mitochondrial activity, migration, and invasion in vitro (P < 0.001).
• In vivo studies demonstrated a significant reduction in tumor growth (P < 0.001) and prevention of metastasis (P < 0.05) with the combination therapy.
• No overt signs of toxicity were observed in the treatment groups.

Conclusions:

• Metformin and propranolol combination therapy exhibits potent antitumor activity against triple-negative breast cancer.
• Drug repositioning of metformin and propranolol presents a promising, non-toxic therapeutic strategy for TNBC.
• Further clinical investigation is warranted to explore the potential of this combination in human TNBC patients.