Bruceine D promotes TNBC regression by inhibiting M2-like tumor-associated macrophage polarization induced Wnt3a/β-catenin pathway

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Triple-negative breast cancer (TNBC) exhibits high invasiveness and recurrence, posing a significant therapeutic challenge.
• Tumor-associated macrophages (TAMs) within the tumor microenvironment are key drivers of TNBC progression.
• Current treatment options for TNBC remain limited.

Purpose of the Study:

• To investigate the therapeutic potential of Bruceine D (BD), a natural quassinoid, against TNBC.
• To elucidate the mechanisms by which BD affects TAMs and Wnt3a/β-catenin signaling in TNBC.

Main Methods:

• Treatment of TNBC models with Bruceine D (BD).
• Assessment of macrophage polarization (M1/M2 ratio) and TAM infiltration.
• Analysis of Wnt3a and β-catenin expression levels.
• Evaluation of tumor growth and metastasis in vivo.

Main Results:

• BD inhibited M2-like macrophage polarization and promoted M1/M2 macrophage ratio.
• BD downregulated Wnt3a secretion and β-catenin expression.
• BD suppressed M2-like macrophage-driven tumor cell proliferation and metastasis.
• BD treatment reduced tumor growth and metastatic lesions in TNBC mouse models.

Conclusions:

• Bruceine D demonstrates significant therapeutic potential for TNBC by modulating TAMs.
• Targeting TAMs and the Wnt3a/β-catenin pathway with BD offers a promising strategy for TNBC treatment.
• BD's ability to remodel the tumor microenvironment warrants further investigation for clinical application.